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1.
Rev. Ciênc. Plur ; 8(3): 27644, out. 2022. ilus, tab
Article in Portuguese | LILACS, BBO | ID: biblio-1399339

ABSTRACT

Introdução:uma vez conhecidos os mecanismos de patogênese do SARS-CoV-2, vários métodos de tratamento para a COVID-19 foram desenvolvidos, dentre eles destaca-se o uso dos anticorpos monoclonais para o contexto de pacientes em estágios graves da doença. Objetivo: compreender se o uso dos anticorpos monoclonais para tratamento da COVID-19 grave interfere nos níveis séricos da angiotensina II. Metodologia:Para a realização dessa pesquisa foram selecionados através do DeCS e MeSH os descritores "COVID-19", "Angiotensin II" e "Antibodies, Monoclonal" e seus respectivos "entry terms" sugeridos pela base MeSH. Posteriormente,utilizando-se os operadores booleanos OR e AND, foi montada uma estratégia de busca, a qual foi utilizada nas bases de dados PUBMED, EMBASE, Web of Science, Cochrane Library e Scopus, sem restrição dedata de publicação ou idioma. Resultados:ao final do processo de seleção dos artigos, 29 foram selecionados para a leitura e análise completa. Nesta revisão, foram abordados diferentes tipos de anticorpos monoclonais, os quais foram oportunamente agrupados de acordo com o seu mecanismo de ação. Conclusão: foi possível concluir que das cinco classes de anticorpos monoclonais tratadas neste trabalho, três potencialmente podem causar alterações nos níveis séricos de angiotensina II (AU).


Introduction:once the mechanisms of pathogenesis of SARS-CoV-2 are known, several methods of treatment for COVID-19 have been developed, among them the use of monoclonal antibodies for the context of patients in severe stages of the disease. Purpose:to understand whether the use of monoclonal antibodies for the treatment of severe COVID-19 interferes with serum angiotensin II levels. Methodology:For this research were selected through DeCS and MeSH the descriptors "COVID-19", "Angiotensin II" and "Antibodies, Monoclonal" and their respective entry "Terms" suggested by the MeSH database. Subsequently, using the boolean operators OR and AND, a search strategy was set up, which was used in the databases PUBMED, EMBASE, Web of Science, Cochrane Library and Scopus, without restriction of publication date or language. Results:at the end of the article selection process, 29 were selected for reading and full analysis. In this review, different types of monoclonal antibodies were addressed, which were opportunely grouped according to their mechanism of action. Conclusion:it was possible to conclude that of the five classes of monoclonal antibodies treated in this study, three potentially can cause changes in serum levels of angiotensin II (AU).


Introducción:Una vez conocidos los mecanismos de patogénesis del SARSCoV-2, se desarrollaron variosmétodos de tratamiento para el COVID-19, entre ellos, el uso de anticuerpos monoclonales para el contexto de pacientes en fases graves de la enfermedad. Objetivo:Comprender si el uso de anticuerpos monoclonales para el tratamiento de la COVID-19 grave interfiere en los niveles séricos de angiotensina II. Metodología:Los descriptores "COVID-19", "Angiotensina II", "Anticuerpos, Monoclonales" y sus respectivos "entry terms" (términos de entrada) sugeridos por el MeSH fueron seleccionados a través de DeCS yMeSH. Posteriormente, utilizando los operadores booleanos OR y AND, se estableció una estrategia de búsqueda que se utilizó en las bases de datos PUBMED, EMBASE, Web of Science, Cochrane Library y Scopus, sin restricción de fecha de publicación ni de idioma. Resultados:Al final del proceso de selección de artículos, se seleccionaron 29 artículos para su lectura y análisis completos. En esta revisión se han abordado diferentes tipos de anticuerpos monoclonales, que se han agrupado oportunamente según su mecanismo de acción. Conclusión:Se pudo concluir que de las cinco clases de anticuerpos monoclonales tratados en este trabajo, tres pueden potencialmente causar alteraciones en los niveles séricos de angiotensina II (AU).


Subject(s)
Angiotensin II , COVID-19/drug therapy , Immunologic Factors/therapeutic use , Antibodies, Monoclonal/therapeutic use , SARS-CoV-2/enzymology
2.
Univ. salud ; 24(2): 184-196, mayo-ago. 2022. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1377466

ABSTRACT

Introducción: El eculizumab es un anticuerpo monoclonal de tipo IgG diseñado para el tratamiento de la hemoglobinuria paroxística nocturna (HPN), en el que su diana farmacológica forma parte del sistema del complemento. Su mecanismo de acción ha permitido implementarlo en el tratamiento de enfermedades huérfanas, como el síndrome urémico hemolítico atípico (SUHa), trastorno del espectro de la neuromielitis óptica (TENMO) y miastenia gravis, cuya incidencia, es baja. Asimismo, es viable en el tratamiento de Guillain Barré y el síndrome antifosfolípido catastrófico (CAPS). Objetivo: Evidenciar aplicaciones terapéuticas del eculizumab y beneficios más significativos en algunos padecimientos. Materiales y métodos: Se realizó búsqueda bibliográfica en el periodo 2010-2021, en bases de datos: Google Scholar, Science Direct, PubMed y Scielo, utilizando como palabra clave "eculizumab". Posteriormente, se afinó la búsqueda utilizando palabras claves asociadas a enfermedades tratadas con este medicamento. Resultados: Se identificó el mecanismo de acción del fármaco y su efecto sobre la patogénesis de hemoglobinuria paroxística nocturna, síndrome urémico atípico, miastenia gravis generalizada refractaria, trastorno del espectro de la neuromielitis óptica, síndromes antifosfolípidos catastrófico y Guillain-Barré. Conclusiones: El eculizumab tiene una alta seguridad y capacidad para tratar y disminuir síntomas de diversas enfermedades que involucran el sistema del complemento.


Introduction: Eculizumab is an IgG type monoclonal antibody designed to treat paroxysmal nocturnal hemoglobinuria (PNH) and its pharmacological target is a member of the complement system. Its mechanism of action has permitted its use in the treatment of orphan diseases such as atypical hemolytic uremic syndrome (aHUS), neuromyelitis optic spectrum disorder (NMOSD), and myasthenia gravis, all of which have a low incidence. Likewise, eculizumab is a viable treatment for Guillain Barré and catastrophic antiphospholipid syndrome (CAS). Objective: To describe the therapeutic applications of eculizumab and its most significant benefits in some illnesses. Materials and methods: A bibliographic search was carried out during the 2010-2021 period in Google Scholar, Science Direct, PubMed and Scielo databases using the keyword eculizumab. Then, the search was refined by using keywords associated with diseases treated with this medication. Results: The mechanism of action of the antibody and its effect on the pathogenesis of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, refractory generalized myasthenia gravis, neuromyelitis optic spectrum disorder, catastrophic antiphospholipid syndrome, and Guillain Barré were identified. Conclusions: Eculizumab has high safety and capacity in treating and diminishing symptoms of diverse illnesses, which involve the complement system.


Subject(s)
Humans , Antibodies, Monoclonal , Immunoglobulins , Hemoglobinuria, Paroxysmal
3.
Rev. cuba. hematol. inmunol. hemoter ; 38(2): e1583, abr.-jun. 2022. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1408455

ABSTRACT

Introducción: Los linfomas no Hodgkin indolentes se destacan por el reto que suponen desde el punto de vista terapéutico. La introducción de la terapia con rituximab, un anticuerpo monoclonal que se une al antígeno CD20 de la membrana de los linfocitos B, revolucionó los tratamientos hasta ese momento y abrió el camino para el desarrollo de otros anticuerpos monoclonales anti-CD20. Objetivo: Describir las características generales de los linfomas no Hodgkin indolentes y de los anticuerpos monoclonales anti-CD20, así como el rol de la terapia anti-CD20 en dichas enfermedades. Métodos: Se realizó una revisión de la literatura publicada en los últimos 20 años, disponible en los repositorios: Scielo, Scopus, Pubmed/Medline, ScienceDirect y Mediagraphic. Se emplearon para elaborar este manuscrito 35 documentos, de ellos 80 por ciento correspondieron a los últimos 5 años. Conclusiones: La sólida evidencia científica, acumulada durante las últimas dos décadas, respalda el uso clínico de los anticuerpos monoclonales anti-CD20 en el tratamiento de los linfomas no Hodgkin indolentes. El uso efectivo de estos fármacos como agentes únicos o combinados con quimioterapia demuestran su versatilidad terapéutica(AU)


Introduction: Indolent non-Hodgkin's lymphomas are notable for the challenge they pose from a therapeutic point of view. The introduction of rituximab, a monoclonal antibody that binds to the CD20 antigen of the B-lymphocyte membrane, revolutionized treatments up to that time and opened the way for the development of other anti-CD20 monoclonal antibodies. Objective: To describe the general characteristics of indolent non-Hodgkin's lymphomas and anti-CD20 monoclonal antibodies, as well as the role of anti-CD20 therapy in these diseases. Methods: A review of the literature published in the last 20 years, available in the repositories: Scielo, Scopus, Pubmed/Medline, Science Direct and Mediagraphic, was performed. Thirty-five papers were used to prepare this manuscript, 80 percent of which corresponded to the last 5 years. Conclusions: Strong scientific evidence, accumulated over the last two decades, supports the clinical use of anti-CD20 monoclonal antibodies in the treatment of indolent non-Hodgkin's lymphomas. The effective use of these drugs as single agents or in combination with chemotherapy demonstrates their therapeutic versatility(AU)


Subject(s)
Humans , Antigens, CD20/therapeutic use , Rituximab , Antibodies, Monoclonal/therapeutic use , Pharmaceutical Preparations
4.
Rev. méd. hondur ; 90(1): 28-35, ene.-jun. 2022. tab.
Article in Spanish | LILACS, BIMENA | ID: biblio-1393003

ABSTRACT

Antecedentes: La pandemia de COVID-19 ha provocado una crisis de salud pública mundial, creando incertidumbre sobre su tratamiento. El Tocilizumab (TCZ), un anticuerpo monoclonal humanizado que actúa como antagonista del receptor de Interleucina 6 (IL-6), ha sido utilizado en enfermedades inmunológicas y en pacientes críticos por COVID-19. Objetivo: Describir el uso de TCZ en pacientes adultos hospitalizados por COVID-19 en Hospital María Especialidades Pediátricas (HMEP), agosto 2020-marzo 2021. Métodos: Estudio descriptivo, retrospectivo. Fuente de datos: expedientes clínicos. Criterios de inclusión: Adulto mayor de 18 años, manejo hospitalario por COVID-19, con TCZ y expediente clínico completo. Criterios de exclusión: Haber recibido TCZ en otro hospital. Se utilizó estadística descriptiva y se realizó análisis de sobrevida de Kaplan & Meier para comparar las probabilidades de sobrevida según edad, con un nivel se significancia p<0.05. Resultados: Se analizaron 104 expedientes clínicos. La mediana de edad de los pacientes fue 57 años (RI=44-67), la edad fue mayor en los pacientes fallecidos; 60% (62/104) del sexo masculino. Los pacientes mostraron mejoría en parámetros clínicos y laboratoriales, como descensos en frecuencia respiratoria y frecuencia cardíaca, aumento de linfocitos y descenso de Proteína C Reactiva (PCR). El análisis de sobrevida de Kaplan & Meier mostró que la probabilidad de vivir en estos pacientes disminuye conforme aumenta la edad. Discusión: Los resultados de este estudio coinciden con los encontrados a nivel internacional, avalando el uso de TCZ en pacientes críticos por COVID-19...(AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , COVID-19/diagnosis , Antibodies, Monoclonal/therapeutic use , Hospitals, Public , Immune System Diseases
5.
Rev. Ciênc. Méd. Biol. (Impr.) ; 21(1): 40-45, maio 05,2022. fig
Article in Portuguese | LILACS | ID: biblio-1370563

ABSTRACT

Introduction: dengue is a most common mosquito-borne viral disease in the Americas and tropical countries. Objective: in this work, mice were hyperimmunized with DENV 4 antigen to produce monoclonal antibodies (mAbs). Methodology: DENV 4 (GenBank KC806069) was inoculated in C6/36 cell monolayers cultivated in Leibovitz's 15 medium supplemented with 5% fetal bovine serum and incubated at 28 oC. The virus stock was submitted to concentration and ultracentrifugation and stored at -80 oC until use (VC DENV 4). Balb/c mice were injected intraperitoneally with 50µg of DENV-4 and successive intraperitoneal injections of 25 µg of VCDENV 4 with Freund's incomplete adjuvant were performed. The spleen cells were fused to SP2/0 myeloma cells with PEG 1540 and distributed in 96-well microplates with Iscove's modified medium with Hipoxantina­Aminopterina­Timidina. Hybridoma screening by indirect ELISA showed positive results for six mAbs, and their characterization was performed by Western blotting and Indirect Immunofluorescence (IFI) techniques. Results: the six mAbs showed strong recognition of prM (24/29 kDa), and minor reaction to E protein (66 kDa), E/E protein dimer (105 kDa), and NS1 (49 kDa) protein in two mAbs. The use of mAbs anti-prM as a diagnostic tool using IFI has been demonstrated to detect DENV-4 antigen in infected cells or tissues. Conclusion: DENV 4 generate mAbs with strong reactivity to prM with potential use to confirm the presence of DENV 4 antigen in tissues or infected cells.


Introdução: a dengue é uma doença viral transmitida por mosquitos comumente das Américas e países tropicais. Objetivo: neste trabalho, camundongos foram hiperimunizados com antígeno DENV 4 para produzir anticorpos monoclonais (mAbs). Metodologia: DENV 4 (GenBank KC806069) foi inoculado em monocamadas de células C6 / 36 cultivadas em meio Leibovitz 15 suplementado com 5% de soro fetal bovino e incubadas a 28oC. O estoque viral foi submetido à concentração, ultracentrifugação e armazenado a -80 oC (VC DENV 4). Camundongos Balb / c foram injetados intraperitonealmente com 50 µg de VC DENV-4 e injeções intraperitoneais sucessivas de 25 µg de antigeno com adjuvante incompleto de Freund. As células do baço foram misturadas a células SP2/0 com PEG 1540 e distribuídas em microplacas de 96 poços com meio Iscove Modificado em presença de Hipoxantina ­ Aminopterina ­ Timidina. A triagem de hibridomas por ELISA indireto apresentou resultados positivos para seis mAbs, e sua caracterização foi realizada por técnicas de Western blotting e Imunofluorescência Indireta (IFI). Resultados: os seis mAbs mostraram forte reconhecimento de prM (24/29 kDa) e reação menor à proteína E (66 kDa), dímero de proteína E / E (105 kDa) e proteína NS1 (49 kDa) em dois mAbs. O uso de mAbs anti-prM como uma ferramenta de diagnóstico utilizando IFI demonstrou eficacia em detectar o antígeno DENV-4 em células ou tecidos infectados. Conclusão: o mAbs produzidos para DENV 4 demonstraram uma forte reatividade contra prM, e poderiam ser uma ferramenta de uso potencial no diagnóstico de DENV 4 .


Subject(s)
Animals , Rats , Dengue , Mice , Antibodies, Monoclonal
6.
s.l; CONETEC; 1 abr. 2022.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-1363200

ABSTRACT

INTRODUCCIÓN: Desarrollado por AstraZeneca, Evusheld es una combinación de dos anticuerpos monoclonales de acción prolongada que funcionan uniéndose a la proteína de pico en el exterior del virus SARS-CoV-2, el virus que causa el COVID-19. Esto, a su vez, evita que el virus se adhiera a las células humanas y entre en ellas. Evusheld se utiliza en pacientes antes de estar expuesto a la infección por COVID-19 para prevenir la enfermedad (lo que se conoce como "profilaxis previa a la exposición"), especialmente en adultos en quienes se considera poco probable que generen una respuesta inmunitaria a partir de la vacunación contra el COVID-19 o para quienes no se recomienda la vacunación.(13) Evusheld es una combinación de tixagevimab (AZD8895) y cilgavimab (AZD1061), derivados de células B donadas por pacientes convalecientes después del virus SARS-CoV-2. Los anticuerpos monoclonales humanos se unen a sitios distintos en la proteína de punta 2 del SARS-CoV-2, con una extensión de la vida media y una unión reducida al receptor Fc. La extensión de la vida media triplica aproximadamente la durabilidad de su acción en comparación con los anticuerpos convencionales y brindaría de seis a doce meses de protección contra COVID-19 luego de una sola administración. El tratamiento se está probando actualmente en varios ensayos de prevención y tratamiento de COVID19: ensayo de fase III PROVENT 8 de más de 5000 participantes en profilaxis previa a la exposición; TACKLE COVID-19 9. Ensayo de tratamiento de fase III en un entorno ambulatorio; y ensayos de tratamiento de colaboradores en entornos ambulatorios y hospitalizados. AZD7442 se está evaluando en las vías de administración IM e intravenosa. (17) Los hallazgos preliminares 'in vitro' de investigadores de la Universidad de Oxford y la Universidad de Columbia también demuestran que AZD7442 neutraliza las variantes virales emergentes recientes del SARS-CoV-2. (18­21) Luego de un parte de prensa en el que se informan los resultados preliminares del estudio STORM-CHASER y PROVENT, para su uso como profilaxis post-exposición y en personas ambulatorias, adultos de alto riesgo en los que resulte poco probable que desarrollen una inmunidad apropiada con la vacunación, su uso fue autorizado por las Agencias de Medicamentos del Reino Unido y los Estados Unidos.(17) La Administración de Drogas y Alimentos (FDA, su sigla del inglés Food and Drugs Administration) de los Estados Unidos emitió una autorización de uso de emergencia para Evusheld para la profilaxis previa a la exposición (prevención) de COVID-19 en personas mayores de 12 años de edad y que pesan al menos 40 kilogramos. (22) El producto solo está autorizado para aquellas personas que actualmente no están infectadas con el virus SARS-CoV-2 y que no han estado expuestas recientemente a una persona infectada con SARS-CoV-2. La autorización también requiere que las personas tengan: sistemas inmunitarios comprometidos de moderados a graves debido a una afección médica, o debido a la toma de medicamentos o tratamientos inmunosupresores, y es posible que no generen una respuesta inmunitaria adecuada a la vacunación contra el COVID-19 o; antecedentes de reacciones adversas graves a una vacuna contra el COVID-19 y/o sus componente. OBJETIVO: El objetivo del presente informe es evaluar parámetros de eficacia, seguridad, conveniencia y recomendaciones disponibles acerca del empleo de la combinación de tixagevimab y cilgavimab (Evusheld) para el tratamiento de pacientes con COVID-19 en Argentina. MÉTODOS: Teniendo en cuenta la velocidad con la que la información relacionada a la pandemia aparece y se modifica, se desarrolló un protocolo sustentado en proyectos que resume activamente la evidencia científica a medida que la misma se hace disponible. Con este fin se utilizó la plataforma L- ove de Epistemonikos https://app.iloveevidence.com/topics para identificar revisiones sistemáticas "vivas". Se seleccionaron aquellas con una calidad metodológica apropiada evaluada a través de la herramienta AMSTAR-2, y que a su vez llevaran un proceso de actualización frecuente. (23) De cada una de las revisiones sistemáticas identificadas se extractaron los efectos de la intervención sobre los desenlaces priorizados como importantes o críticos y la certeza en dichos efectos. Para la priorización de los desenlaces se adoptó una perspectiva desde el paciente considerando sus potenciales preferencias. La selección se realizó por consenso entre los autores y supervisores del informe considerando los resultados de múltiples ejercicios de priorización publicados, realizados en el marco del desarrollo de distintas guías de práctica clínica. Se seleccionaron "mortalidad", "ingreso en asistencia ventilatoria mecánica", "tiempo hasta resolución de síntomas", "hospitalización", "eventos adversos graves" como desenlaces críticos. Adicionalmente, se extractaron datos relacionados con efectos de subgrupo potencialmente relevantes para la toma de decisión, con especial énfasis en el tiempo de evolución, la severidad de la enfermedad y el estado de vacunación. En los casos en que no fue reportado por las revisiones sistemáticas incluidas, se calculó el efecto absoluto de las intervenciones en pacientes vacunados, tomando el riesgo basal reportado para pacientes no vacunados multiplicado por un riesgo relativo de 0,1 según el efecto de la vacunación observado en distintos estudios y sistemas de vigilancia. (8,10,24,25) Para confeccionar las conclusiones en el efecto de las intervenciones evaluadas sobre los desenlaces priorizados, utilizamos lineamientos publicados, específicamente desarrollados a tal fin. Este dominio contempla dos subdominios: la existencia de barreras y facilitadores en nuestro contexto para la implementación de la tecnología evaluada no consideradas en los otros dominios analizados, y los costos comparativos en relación con otras intervenciones similares. Con el objetivo de emitir un juicio de valor sobre la magnitud de dichos costos, en pacientes hospitalizados se utilizó como comparador al tratamiento con dexametasona, que ha demostrado ser una intervención accesible y de beneficios importantes en el contexto analizado. Para la identificación de recomendaciones sustentadas en evidencia y actualizadas, se utilizó la plataforma COVID recmap. Se seleccionaron aquellas guías con rigor metodológico apropiado según la herramienta AGREE II (> 70%) y se incorporaron sus recomendaciones al informe. RESULTADOS: No se identificaron revisiones sistemáticas que cumplieran con los criterios de inclusión del presente informe y reportaron resultados. El ensayo STORM CHASER, cuyos resultados preliminares fueron publicados en un parte de prensa por el laboratorio AstraZeneca, evaluó la seguridad y eficacia de AZD7442, una combinación de anticuerpos de acción prolongada, para la prevención de la COVID-19 sintomática en participantes expuestos recientemente al virus SARS-CoV-2. El ensayo no cumplió con el criterio principal de valoración de la prevención posterior a la exposición de la COVID-19 sintomática con AZD7442 en comparación con el placebo. Los participantes del ensayo eran adultos no vacunados de 18 años o más con exposición confirmada a una persona con un caso del virus SARS-CoV-2 en los últimos ocho días. Adicionalmente, existe información sobre la efectividad in vitro de tixagevimab/cilgavimab frente a las diferentes variantes de SARS-CoV-2. Esta información se encuentra disponible en OpenData Portal, que condensa la información de un conjunto priorizado de publicaciones (preprints y artículos revisados por pares). Los resultados muestran que la combinación de tixagevimab/cilgavimab podría ser menos activa frente a las nuevas variantes del SARS-CoV-2, incluida Omicrón y subvariantes (B.1.1.529; BA.1.1; BA.1; BA.1 [+Q493K]; BA.2; B.1.1.529 [+F694Y] en comparación de las variantes predominantes al momento de realizarse el estudio STORM-CHASER. CONCLUSIONES: El cuerpo de la evidencia (un estudio aún no publicado cuyos datos se encuentran parcialmente disponibles en un comunicado de prensa) muestra que tixagevimab/cilgavimab, podría tener un beneficio clínico pequeño en personas expuestas al SARS-COV-2 con factores de riesgo para progresar a enfermedad grave que no han sido vacunados y con riesgo de falla inmune. En esta población, podría disminuir el riesgo de infección. No se cuenta con datos de infección por nuevas variantes ni relacionados con otros desenlaces como la admisión hospitalaria, la necesidad de ventilación mecánica o la muerte. Esta tecnología tampoco ha sido probada en personas vacunadas ni en otros escenarios. La evidencia proveniente de estudios in vitro, nos muestra que podría no ser activa frente a las nuevas variantes del SARS-CoV-2, incluida Omicrón y sus sub-variantes en estudio. La tecnología no está autorizada para su comercialización por la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica de nuestro país. La forma de administración y el costo comparativo estimado es elevado podrían constituir barreras para su uso. Las guías de práctica clínica de alta calidad metodológica actualizadas no tienen una dirección clara en cuanto a la utilización rutinaria del tratamiento y sugieren utilizar el tratamiento en casos muy especiales en personas de alto riesgo muy seleccionadas para profilaxis previa a la exposición.


Subject(s)
Humans , SARS-CoV-2/drug effects , COVID-19/drug therapy , Antibodies, Monoclonal/therapeutic use , Argentina , Efficacy , Cost-Benefit Analysis
7.
Lima; Instituto Nacional de Salud; feb. 2022.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-1369710

ABSTRACT

ANTECEDENTES: Este informe se efectúa en atención a la solicitud la jefatura del Instituto Nacional de Salud (INS). El 8 de diciembre de 2021, la FDA emitió la autorización de uso de emergencia de la combinación de anticuerpos monoclonales tixagevimab y cilgavimab (Evusheld) como profilaxis pre exposición (prevención) en cierta población de adultos y niños (personas inmunocomprometidas y antecedentes de reacciones adversas severas a las vacunas contra COVID-19) (1). La EMA continua con el proceso de revisión de la eficacia y seguridad (2). El objetivo es sintetizar la evidencia científica publicada respecto a la eficacia y seguridad de la combinación de tixagevimab y cilgavimab (EvusheldTM) contra la COVID-19. MÉTODOS: Pregunta PICO: ¿En población con COVID-19, cuál es la eficacia y seguridad de la combinación de de tixagevimab y cilgavimab (Evusheld)? Criterios de elegibilidad: Los criterios de selección de los estudios fueron los siguientes: Ensayos clínicos aleatorizados o revisiones sistemáticas que reporten resultados para al menos uno de los desenlaces. En ausencia de resultados de eficacia para alguno de los desenlaces, se considerará los resultados de efectividad a partir de estudios de cohorte o test negativo. Estudios publicados en idioma inglés y español. Se excluyeron cartas al editor, revisiones narrativas, estudios preclínicos (estudios in vitro o en modelos animales), artículos de opinión y manuscritos no revisados por pares. Métodos para la búsqueda e identificación de la evidencia: Los ensayos clínicos fueron identificados desde las siguientes fuentes (búsqueda realizada el 3 de febrero de 2022): Plataforma Living Overview of the Evidence (L·OVE) de la Fundación Epistemonikos (https://www.epistemonikos.org/en/). Bases de datos electrónicas: MEDLINE/Pubmed, Embase y Cochrane Library. Registro de Ensayos Clínicos de Estados Unidos (https://clinicaltrials.gov/ct2/home) y la Plataforma Internacional de Registro de Ensayos Clínicos de la OMS (https://trialsearch.who.int/). Páginas institucionales de la Food and Drug Administration (FDA) de Estados Unidos (https://www.fda.gov/) y la European Medicines Agency (EMA) (https://www.ema.europa.eu/en). RESULTADOS: No se encontraron ECA o RS en las bases de datos seleccionadas que muestren resultados de eficacia o seguridad de la combinación de tixagevimab y cilgavimab (Evusheld). En cambio, se encontraron 8 protocolos de ECA que están en progreso. CONCLUSIONES: La presente nota técnica tiene como objetivo sintetizar la evidencia disponible sobre la eficacia y seguridad de la combinación de tixagevimab y cilgavimab (Evusheld) para la prevención de la infección por SARS-CoV-2. En la búsqueda de información, no se encontraron ECA o RS publicados en revistas científicas que mostraran información sobre la eficacia y seguridad de la combinación de tixagevimab y cilgavimab (Evusheld). En cambio, se encontró una revisión de la FDA de la ECA PROVENT que evaluó la eficacia y seguridad de la combinación de tixagevimab y cilgavimab (Evusheld). La combinación de tixagevimab y cilgavimab (Evusheld) fue evaluada en población que fue candidata a inmunización pasiva con anticuerpos, en este grupo se incluyeron las personas que tuvieron una respuesta deficiente a vacunas o personas con riesgo incrementado a infección por SARS-CoV-2. Según el informe, combinación de tixagevimab y cilgavimab (Evusheld) mostró una reducción del riesgo relativo en la infección sintomática por SARS-CoV-2 (confirmado por RT-PCR) de 76.7%. La combinación de tixagevimab y cilgavimab (Evusheld) mostró una reducción del riesgo relativo de muerte por cualquier causa de 68.8%. Se ha reportado eventos adversos asociados a tratamiento en el grupo intervención (8%) y en el grupo placebo (7%). Se ha reportado eventos adversos con desenlace de muerte en el grupo AZD7442 (0.12%) y placebo (0.23%), los detalles de estos desenlaces no están disponibles en el reporte. Los eventos adversos de especial interés fueron reportados en el grupo AZD7442 (3%) y en el grupo placebo (2%).


Subject(s)
Humans , SARS-CoV-2/drug effects , COVID-19/drug therapy , Antibodies, Monoclonal/therapeutic use , Drug Combinations
8.
Rev. Bras. Cancerol. (Online) ; 68(3)Jul-Set. 2022.
Article in Portuguese | LILACS, ColecionaSUS | ID: biblio-1411254

ABSTRACT

Introdução: A utilização dos anticorpos monoclonais vem sendo incorporada aos protocolos de tratamento para câncer, uma vez comprovada sua eficácia. Essa modalidade de terapia é onerosa, e sua aquisição ainda constitui um obstáculo para o paciente. Objetivo: Descrever a utilização de anticorpos monoclonais no que tange à forma de aquisição, regulação e judicialização, efeitos adversos e causas de interrupção da terapia. Método: Estudo descritivo com avaliação de pacientes (n=169) em tratamento para câncer, em um hospital público, no período de 1 de agosto de 2017 a 31 de julho de 2019. Resultados: A população estudada foi majoritariamente feminina (n=115). As principais neoplasias encontradas foram de mama (n=64, 36,16%), linfomas (n=53, 29,94%) e mieloma múltiplo de plasmócito/plasmocitoma (n=25, 14,12%). Os anticorpos monoclonais mais utilizados foram o trastuzumabe (n=65, 35,71%) e rituximabe (n=54, 29,67%). Foram observadas quatro formas de aquisição dos fármacos. As aquisições por meio do Sistema Único de Saúde (SUS) (n=103, 56,59%) e judicial (n=72, 39,56%) prevaleceram. A maioria dos pacientes não apresentou efeitos adversos à terapia (60,3%); mas, entre os que apresentaram, os principais efeitos foram vômitos e náuseas, astenia, diarreia, dor, neutropenia e mucosite. Efeitos adversos/toxicidade (n=15), falta de medicamento (n=11) e atraso na liberação (n=10) foram as causas mais comuns de interrupção do tratamento. Conclusão: Os anticorpos monoclonais são mais específicos e apresentam menores efeitos. Aos fármacos indisponíveis pelo SUS, a judicialização mostra-se como uma ferramenta importante


Introduction: The use of monoclonal antibodies has been incorporated into cancer treatment protocols, once their effectiveness has been proven. This type of therapy is costly and its acquisition is still an obstacle for the patient. Objective: To describe the use of monoclonal antibodies in the perspective of purchasing, regulation and judicialization, adverse effects and causes of therapy discontinuation. Method: Descriptive study evaluating patients (n=169) undergoing treatment for cancer in a public hospital, from August 1, 2017 to July 31, 2019. Results: The population investigated consisted mostly of females (n=115). The main neoplasms found were breast (n=64, 36.16%), lymphomas (n=53, 29.94%) and plasma cell/plasmacytoma multiple myeloma (n=25, 14.12%). The most used monoclonal antibodies were trastuzumab (n=65, 35.71%) and rituximab (n=54, 29.67%). Four forms of drug purchase were observed. The purchases through the National Health System (SUS) (n=103, 56.59%) and law-mandated (n=72, 39.56%) prevailed. Most patients had no therapy-related adverse effects (60.3%), but among those who did, the main effects were vomiting and nausea, asthenia, diarrhea, pain, neutropenia and mucositis. Adverse effects/toxicity (n=15), lack of medication (n=11) and delayed approval (n=10) were the most common causes of treatment discontinuation. Conclusion: Monoclonal antibodies are more specific and have lesser effects. For drugs unavailable at SUS, judicialization is an important tool


Introducción: El uso de anticuerpos monoclonales se ha incorporado a los protocolos de tratamiento del cáncer, una vez comprobada su eficacia. Este tipo de terapia es costosa y su adquisición sigue siendo un obstáculo para el paciente. Objetivo: Describir el uso de anticuerpos monoclonales en términos de adquisición, regulación y judicialización, efectos adversos y causas de interrupción de la terapia. Método: Estudio descriptivo que evaluó a pacientes (n=169) en tratamiento por cáncer, en un hospital público, desde el 1 de agosto de 2017 al 31 de julio de 2019. Resultados: La población estudiada fue mayoritariamente femenina (n=115). Las principales neoplasias encontradas fueron mama (n=64, 36,16%), linfomas (n=53, 29,94%) y mieloma múltiple de células plasmáticas/plasmocitomas (n=25, 14,16%). Los anticuerpos monoclonales más utilizados fueron trastuzumab (n=65, 35,71%) y rituximab (n=54, 29,67%). Se observaron cuatro formas de adquisición de fármacos. Predominaron las adquisiciones a través del Sistema Único de Salud (SUS) (n=103, 56,59%) y judiciales (n=72, 39,56%). La mayoría de los pacientes no presentaron efectos adversos a la terapia (60,3%), pero entre los que sí los tuvieron, los principales efectos fueron vómitos y náuseas, astenia, diarrea, dolor, neutropenia y mucositis. Los efectos adversos/toxicidad (n=15), la falta de medicación (n=11) y la liberación retardada (n=10) fueron las causas más frecuentes de interrupción del tratamiento. Conclusión: Los anticuerpos monoclonales son más específicos y tienen menos efectos. Para los medicamentos no disponibles en el SUS, la judicialización es una herramienta importante


Subject(s)
Pharmaceutical Services , Health's Judicialization , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Neoplasms/drug therapy
9.
Rev. Bras. Cancerol. (Online) ; 68(3)Jul-Set. 2022.
Article in Portuguese | LILACS, ColecionaSUS | ID: biblio-1412020

ABSTRACT

Introdução: A utilização dos anticorpos monoclonais vem sendo incorporada aos protocolos de tratamento para câncer, uma vez comprovada sua eficácia. Essa modalidade de terapia é onerosa, e sua aquisição ainda constitui um obstáculo para o paciente. Objetivo: Descrever a utilização de anticorpos monoclonais no que tange à forma de aquisição, regulação e judicialização, efeitos adversos e causas de interrupção da terapia. Método: Estudo descritivo com avaliação de pacientes (n=169) em tratamento para câncer, em um hospital público, no período de 1 de agosto de 2017 a 31 de julho de 2019. Resultados: A população estudada foi majoritariamente feminina (n=115). As principais neoplasias encontradas foram de mama (n=64, 36,16%), linfomas (n=53, 29,94%) e mieloma múltiplo de plasmócito/plasmocitoma (n=25, 14,12%). Os anticorpos monoclonais mais utilizados foram o trastuzumabe (n=65, 35,71%) e rituximabe (n=54, 29,67%). Foram observadas quatro formas de aquisição dos fármacos. As aquisições por meio do Sistema Único de Saúde (SUS) (n=103, 56,59%) e judicial (n=72, 39,56%) prevaleceram. A maioria dos pacientes não apresentou efeitos adversos à terapia (60,3%); mas, entre os que apresentaram, os principais efeitos foram vômitos e náuseas, astenia, diarreia, dor, neutropenia e mucosite. Efeitos adversos/toxicidade (n=15), falta de medicamento (n=11) e atraso na liberação (n=10) foram as causas mais comuns de interrupção do tratamento. Conclusão: Os anticorpos monoclonais são mais específicos e apresentam menores efeitos. Aos fármacos indisponíveis pelo SUS, a judicialização mostra-se como uma ferramenta importante


Introduction: The use of monoclonal antibodies has been incorporated into cancer treatment protocols, once their effectiveness has been proven. This type of therapy is costly and its acquisition is still an obstacle for the patient. Objective: To describe the use of monoclonal antibodies in the perspective of purchasing, regulation and judicialization, adverse effects and causes of therapy discontinuation. Method: Descriptive study evaluating patients (n=169) undergoing treatment for cancer in a public hospital, from August 1, 2017 to July 31, 2019. Results: The population investigated consisted mostly of females (n=115). The main neoplasms found were breast (n=64, 36.16%), lymphomas (n=53, 29.94%) and plasma cell/plasmacytoma multiple myeloma (n=25, 14.12%). The most used monoclonal antibodies were trastuzumab (n=65, 35.71%) and rituximab (n=54, 29.67%). Four forms of drug purchase were observed. The purchases through the National Health System (SUS) (n=103, 56.59%) and law-mandated (n=72, 39.56%) prevailed. Most patients had no therapy-related adverse effects (60.3%), but among those who did, the main effects were vomiting and nausea, asthenia, diarrhea, pain, neutropenia and mucositis. Adverse effects/toxicity (n=15), lack of medication (n=11) and delayed approval (n=10) were the most common causes of treatment discontinuation. Conclusion: Monoclonal antibodies are more specific and have lesser effects. For drugs unavailable at SUS, judicialization is an important tool


Introducción: El uso de anticuerpos monoclonales se ha incorporado a los protocolos de tratamiento del cáncer, una vez comprobada su eficacia. Este tipo de terapia es costosa y su adquisición sigue siendo un obstáculo para el paciente. Objetivo: Describir el uso de anticuerpos monoclonales en términos de adquisición, regulación y judicialización, efectos adversos y causas de interrupción de la terapia. Método: Estudio descriptivo que evaluó a pacientes (n=169) en tratamiento por cáncer, en un hospital público, desde el 1 de agosto de 2017 al 31 de julio de 2019. Resultados: La población estudiada fue mayoritariamente femenina (n=115). Las principales neoplasias encontradas fueron mama (n=64, 36,16%), linfomas (n=53, 29,94%) y mieloma múltiple de células plasmáticas/plasmocitomas (n=25, 14,16%). Los anticuerpos monoclonales más utilizados fueron trastuzumab (n=65, 35,71%) y rituximab (n=54, 29,67%). Se observaron cuatro formas de adquisición de fármacos. Predominaron las adquisiciones a través del Sistema Único de Salud (SUS) (n=103, 56,59%) y judiciales (n=72, 39,56%). La mayoría de los pacientes no presentaron efectos adversos a la terapia (60,3%), pero entre los que sí los tuvieron, los principales efectos fueron vómitos y náuseas, astenia, diarrea, dolor, neutropenia y mucositis. Los efectos adversos/toxicidad (n=15), la falta de medicación (n=11) y la liberación retardada (n=10) fueron las causas más frecuentes de interrupción del tratamiento. Conclusión: Los anticuerpos monoclonales son más específicos y tienen menos efectos. Para los medicamentos no disponibles en el SUS, la judicialización es una herramienta importante


Subject(s)
Humans , Female , Pharmaceutical Services , Health's Judicialization , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/drug effects , Neoplasms/drug therapy
10.
Chinese Journal of Lung Cancer ; (12): 468-476, 2022.
Article in Chinese | WPRIM | ID: wpr-939733

ABSTRACT

Antibody drug conjugates (ADCs) are a novel class of anti-cancer drugs, which combined the specificity of monoclonal antibodies with the cytotoxic palyload via the linkers. Many ADCs have not only verified impressive activity in a variety of cancers, including breast cancer and hematological system tumors, but also in lung cancer. The aim of this study was to provide informations for practice by summarizing the mechanism of action, clinical application and problems and challenges of ADCs.
.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Humans , Immunoconjugates/therapeutic use , Lung Neoplasms/drug therapy , Neoplasms/drug therapy
11.
Article in Chinese | WPRIM | ID: wpr-939704

ABSTRACT

OBJECTIVE@#To establish a new method for synthesizing Lewis blood group antigens, that is, the mimotopes of Lewis blood group antigens were screened by using an alpaca phage display nanobody library.@*METHODS@#We selected mimotopes of the Lewis a (lea) antigen by affinity panning of an alpaca phage display nanobody library using a monoclonal anti-lea antibody. Enzyme-linked immunosorbent assay (ELISA) was used to test the affinity of the positive clones for the monoclonal anti-lea antibody, and the high-affinity positive clones were selected for sequencing and synthesis. Finally, the sensitivity, specificity and reactivity of the synthesized lea mimotope in clinical samples were verified by ELISA.@*RESULTS@#A total of 96 phage clones were randomly selected, and 24 were positive. Fourteen positive clones with the highest affinity were selected for sequencing. The result showed that there were 5 different sequences, among which 3 sequences with the highest frequency, largest difference and highest affinity were selected for expression and synthesis. The sensitivity and specificity of lea mimic antigen by ELISA showed that, the minimum detection limit of gel microcolumn assay (GMA) and ELISA method were 25 times different, and the lea mimic antigen had no cross reacted with the other five unrelated monoclonal antibodies(P<0.001). Finally, 30 clinical plasma samples were analyzed. The mean absorbance of the 15 positive plasma samples was significantly higher than that of the 15 negative plasma samples (P=0.02). However, the positive signal values of the clinical samples were much lower than those of the monoclonal antibodies.@*CONCLUSION@#A new method of screening lea mimic antigen by using alpaca phage nanoantibody library has been established, which is expected to realize the screening of lea mimotopes, thus realizing the application of high-sensitivity detection methods such as ELISA and chemiluminescence in blood group antibody identification.


Subject(s)
Animals , Antibodies, Monoclonal , Antineoplastic Agents, Immunological , Bacteriophages , Blood Group Antigens , Camelids, New World , Enzyme-Linked Immunosorbent Assay/methods , Epitopes , Humans , Lewis Blood Group Antigens , Peptide Library
12.
Article in Chinese | WPRIM | ID: wpr-935254

ABSTRACT

The epidermal growth factor receptor (EGFR) signaling is aberrantly overexpressed in many solid malignancies, making it an important target for anti-cancer biologic agents. Among them, epidermal growth factor receptor inhibitors (EGFRIs), which have been widely used in clinical practice, include anti-EGFR monoclonal antibodies and tyrosine kinase inhibitors. A proportion of patients treated with EGFRIs develop specific, dose-dependent skin toxicity such as papulopustular rash, paronychia, xerosis and itch. These side effects can cause physical and psychosocial discomfort that may result in dose reduction, discontinuance, or replacement of the current EGFRIs treatment. Correct diagnosis and treatment of these skin and mucosal adverse effects associated with EGFRIs is of great significance for the tertiary prevention of malignant tumors. A review on EGFRI-related mucocutaneous adverse reactions is presented here, focusing on the pathogenesis, the various clinical manifestations, the strategies for prevention and treatment of these conditions.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/therapeutic use , ErbB Receptors/therapeutic use , Humans , Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use
13.
Chinese Journal of Hematology ; (12): 400-407, 2022.
Article in Chinese | WPRIM | ID: wpr-929627

ABSTRACT

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.


Subject(s)
Antibodies, Monoclonal/pharmacology , Graft vs Host Disease/metabolism , Hematopoietic Stem Cell Transplantation , Humans , Killer Cells, Natural , Retrospective Studies , Treatment Outcome
14.
Chinese Journal of Hematology ; (12): 31-34, 2022.
Article in Chinese | WPRIM | ID: wpr-929526

ABSTRACT

Objective: The study investigated the efficacy and safety of daratumumab in the treatment of cardiac light chain (AL) amyloidosis. Methods: We retrospectively analyzed the clinical characteristics, hematologic response, organ response, long-term survival, and adverse events of 20 patients with newly diagnosed or relapsed/refractory cardiac AL amyloidosis treated with daratumumab in Peking Union Medical College Hospitalo from January 2017 to March 2021. Results: The overall median age of 20 patients was 62 (range, 45-73) yeas, with a male to female ratio of 2.3:1. Nine patients were newly diagnosed, while 11 patients had relapsed or refractory disease. Based on Mayo 2004 cardiac AL staging system, stages Ⅱ and Ⅲ diseases were present in 20 patients respectively. Four patients died during the first cycle of daratumumab, and the remaining 16 patients completed a median of 3 (range, 1-10) cycles of treatment. Overall hematologic response rates were 80% each at 1, 3, and 6 months after treatment initiation, and 45% , 60% , and 60% of the patients achieved at least a very good partial response at 1, 3, and 6 months respectively. The median duration to hematologic response was 13 (range, 6-28) days. At 3, 6, and 12 months, 20% , 30% , and 40% of the patients respectively achieved a cardiac response, and the median days to response was 91 (range, 30-216) days. As of the last follow-up, 9 (45% ) patients died. The 1-month mortality rate of all the patients and stage IIIb patients was 25% and 40% , respectively. The 1-year overall survival rate was 48.4% . Lymphocytopenia was the most common hematological adverse event (above grade 3) . Non-hematological adverse events were mainly infusion-related reactions and infections. Conclusion: Daratumumab could induce deep and rapid hematologic response in newly diagnosed and previously treated cardiac AL amyloidosis patients. However, daratumumab was not effective in preventing the high and early mortality rate in stage Ⅲb patients.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Immunoglobulin Light-chain Amyloidosis/drug therapy , Male , Retrospective Studies , Treatment Outcome
15.
Chinese Journal of Lung Cancer ; (12): 214-218, 2022.
Article in Chinese | WPRIM | ID: wpr-928800

ABSTRACT

Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world. Non-small cell lung cancer (NSCLC) is one of the most important pathological types of lung cancer. The prognosis of advanced NSCLC is poor and medical treatment is still the main treatment option. Antibody-drug conjugates (ADCs) are the kind of potentially new anti-tumor drugs, consisting of monoclonal antibodies conjugated to the cytotoxic payloads via the synthetic linkers. They have a broad application prospect in solid tumors such as lung cancer. This article focuses on the mechanism of action and research progress of ADCs in advanced NSCLC.
.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immunoconjugates/therapeutic use , Lung Neoplasms/drug therapy
16.
Article in Chinese | WPRIM | ID: wpr-927910

ABSTRACT

Puerarin was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) by periodate oxidation to serve as the immunogen and coating antigen, respectively. BALB/c mice were immunized with puerarin-BSA according to the routine immunization procedure, and the titer and specificity of serum were detected after three immunization. After booster immunization, mouse spleen lymphocytes were fused with mouse myeloma cells, and 24 hybridoma cell lines of the monoclonal antibodies against puerarin were screened by monoclonal antibody screening technique. Ascites was prepared and purified. The cross-reactivity of monoclonal antibody(mAb) M1 with 4'-methoxy puerarin, daidzin, puerarin-6″-O-xyloside, daidzein, mirificin, 3'-methoxy puerarin, and 3'-hydroxy puerarin was 239.84%, 112.18%, 67.89%, 58.28%, 22.37%, 0.40%, and 0.20%, respectively, and those with other analogs such as baicalein and baicalin were all less than 0.10%. The IC_(50) and the working range of the indirect competitive enzyme-linked immunosorbent assay(icELISA) for puerarin were 44.80 ng·mL~(-1) and 8.20-292.30 ng·mL~(-1), respectively. The average recovery was 91.95%-98.20% with an RSD in the range of 0.70%-2.60%. The content of puerarin in different Puerariae Lobatae Radix samples was determined with icELISA and validated by UPLC-MS. The correlation between data obtained from icELISA and UPLC-MS was 0.999 0, indicating that icELISA is suitable for the rapid detection of puerarin in Puerariae Lobatae Radix samples.


Subject(s)
Animals , Antibodies, Monoclonal , Chromatography, Liquid , Enzyme-Linked Immunosorbent Assay/methods , Hybridomas/metabolism , Isoflavones , Mice , Mice, Inbred BALB C , Tandem Mass Spectrometry
17.
Chinese Journal of Biotechnology ; (12): 1197-1208, 2022.
Article in Chinese | WPRIM | ID: wpr-927774

ABSTRACT

8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive and stable biomarker for evaluating DNA oxidative damage. A rapid and sensitive colloidal gold immunochromatographic strip was developed for 8-OHdG detection by a competitive method. The sample pad (glass cellulose film), bonding pad (glass cellulose film), nitrocellulose film and absorbent pad were pasted on the polyvinyl chloride (PVC) base plate to construct the test strip. Colloidal gold (AuNPs) was prepared by the reduction of chloroauric acid with sodium citrate. 8-OHdG antibody (Ab) was coated on the outer layer of AuNPs to form Ab@AuNPs as a probe. Bovine serum albumin (BSA) and 8-OHdG were conjugated with carbodiimide hydrochloride to prepare an artificial antigen, which was used as the coating antigen of detection line. Goat anti mouse polyclonal antibody IgG was used as the coating antibody of control line. The experimental parameters were optimized including the type of nitrocellulose membrane, the formula of loading solution, and the spraying amount of gold labeled antibody. The results showed that the appropriate nitrocellulose membrane was CN 95. The optimal loading solution included BSA (1%), Tween-20 (3%), sucrose (3%) and NaCl (0.9%). The optimal spraying amount of gold labeled antibody was 4 μL. 8-OHdG can be detected by the strip under visible light, and the level of 8-OHdG in urine can be preliminarily determined by comparing the color intensity of T line and C line. The 8-OHdG concentration in urine was further calculated by the gray value of T line and the threshold of detection was 2.55 μg/L. This colloidal gold immunochromatographic strip is simple, rapid and specific for detecting 8-OHdG in human urine to preliminarily evaluate the human status.


Subject(s)
8-Hydroxy-2'-Deoxyguanosine , Animals , Antibodies, Monoclonal , Gold , Gold Colloid/chemistry , Metal Nanoparticles , Mice , Sensitivity and Specificity
18.
Chinese Journal of Biotechnology ; (12): 185-195, 2022.
Article in Chinese | WPRIM | ID: wpr-927703

ABSTRACT

Clostridium difficile is an important zoonotic intestinal pathogen, which is widely present in humans and a variety of animals. The ST11 type C. difficile is one of the most widespread and harmful subtypes in the world. As a large country in pig farming, China lacks efficient methods for detecting C. difficile of porcine origin, leaving hidden dangers for the prevention and control of C. difficile. The aim of this study was to develop a specific and sensitive double-antibody sandwich ELISA for the epidemiological investigation of ST11 type C. difficile of porcine origin. Firstly, a 97 kDa receptor binding domain (RBD) was expressed in a prokaryotic host and purified. A hybridoma cell line AE2D3 capable of stably secreting monoclonal antibody targeting the RBD was screened, and the antibody subtype was determined to be IgG2b (κ). Secondly, a double antibody sandwich ELISA method was developed, where the monoclonal antibody targeting the RBD was used as a detection antibody, and the rabbit polyclonal antibody was used as a capture antibody. The chessboard method was used to determine the matching concentration of the capture antibody and the detection antibody, the antigen coating conditions, the blocking conditions, the incubation conditions for detection antibody and samples to be tested, as well as the reaction conditions of HRP-conjugated and reaction conditions of TMB chromogenic solution. The negative cutoff OD450 was 0.152, and no cross-reaction with 13 strains of non-ST11 type C. difficile was found. The minimum detection concentration of RBD was 8.83 ng/mL. This specific and sensitive double-antibody sandwich ELISA provides a reliable serological detection method for epidemiological investigation of the ST11 type C. difficile in pig industry.


Subject(s)
Animals , Antibodies, Monoclonal , Bacterial Proteins/genetics , Bacterial Toxins , Clostridioides difficile , Enzyme-Linked Immunosorbent Assay , Hybridomas , Swine
19.
Chinese Journal of Biotechnology ; (12): 160-173, 2022.
Article in Chinese | WPRIM | ID: wpr-927701

ABSTRACT

The conserved hemagglutinin (HA) stem region of avian influenza virus (AIV) is an important target for designing broad-spectrum vaccines, therapeutic antibodies and diagnostic reagents. Previously, we obtained a monoclonal antibody (mAb) (5D3-1B5) which was reactive with the HA stem epitope (aa 428-452) of H7N9 subtype AIV. To systematically characterize the mAb, we determined the antibody titers, including the HA-binding IgG, hemagglutination-inhibition (HI) and virus neutralizing (VN) titers. In addition, the antigenic epitope recognized by the antibody as well as the sequence and structure of the antibody variable region (VR) were also determined. Moreover, we evaluated the cross-reactivity of the antibody with influenza virus strains of different subtypes. The results showed that the 5D3-1B5 antibody had undetectable HI and VN activities against H7N9 virus, whereas it exhibited strong reactivity with the HA protein. Using the peptide-based enzyme-linked immunosorbent assay and biopanning with a phage-displayed random peptide library, a motif with the core sequence (431W-433Y-437L) in the C-helix domain in the HA stem was identified as the epitope recognized by 5D3-1B5. Moreover, the mAb failed to react with the mutant H7N9 virus which contains mutations in the epitope. The VR of the antibody was sequenced and the complementarity determining regions in the VR of the light and heavy chains were determined. Structural modeling and molecular docking analysis of the VR verified specific binding between the antibody and the C-helix domain of the HA stem. Notably, 5D3-1B5 showed a broad cross-reactivity with influenza virus strains of different subtypes belonging to groups 1 and 2. In conclusion, 5D3-1B5 antibody is a promising candidate in terms of the development of broad-spectrum virus diagnostic reagents and therapeutic antibodies. Our findings also provided new information for understanding the epitope characteristics of the HA protein of H7N9 subtype AIV.


Subject(s)
Animals , Antibodies, Monoclonal , Antibodies, Viral , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinins , Influenza A Virus, H7N9 Subtype , Influenza in Birds , Molecular Docking Simulation
20.
Chinese Medical Journal ; (24): 799-805, 2022.
Article in English | WPRIM | ID: wpr-927570

ABSTRACT

BACKGROUND@#The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.@*METHODS@#H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.@*RESULTS@#The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.@*CONCLUSION@#The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.


Subject(s)
Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral , Hemagglutinins , Humans , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H3N2 Subtype , Influenza A Virus, H7N9 Subtype , Influenza Vaccines , Influenza in Birds , Influenza, Human/prevention & control , Mice
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