Análisis de mutaciones BRAF y NRAS de tumores tiroideos en pacientes de Argentina / Analysis of BRAF and NRAS mutations in thyroid tumors in patients from Argentina

Resumen Introducción : Se ha descrito que alteraciones molecu lares de las células foliculares tiroideas en el gen BRAF o en NRAS están asociadas con el proceso de carcinogé nesis. Nuestro objetivo fue conocer la frecuencia muta cional de BRAF y NRAS a partir de muestras de punción aspirativa con aguja fina (PAAF) en nuestra población. Métodos : Se analizó por qPCR el estado mutacional de BRAF (codón 600) y NRAS (codón 61) de 193 mues tras obtenidas por PAAF de nódulos sospechosos y se comparó con los datos de la anatomía patológica de 115 pacientes. Resultados : La mutación BRAF se identificó en 40 muestras (74.1%) de las punciones categorizadas como Bethesda VI (n = 54). En las muestras que se correspon dieron con carcinoma papilar de tiroides (CPT) variante clásica por histología (n = 47), el 70% presentó la muta ción, mientras que en los otros subtipos la prevalencia fue más baja (p = 0.013). En muestras de lesión folicular (n = 36), el 50% de los carcinomas foliculares resultaron positivos para NRAS pero solo el 6.7% de los adenomas presentaron esta variación. La presencia de mutación BRAF y CPT se asociaron con metástasis en los gan glios linfáticos (p = 0.014) y mayor riesgo relativo de recurrencia según el Consenso Argentino Intersocietario (RR = 6.77, p = 0.022). No hubo diferencias significativas entre la mutación de BRAF y otras características de agresividad en CPT. Conclusión : La mutación de BRAF y NRAS se observa en un número significativo de CPT y carcinoma folicular, respectivamente, en nuestra población. La mutación BRAF se correlaciona significativamente con metástasis en los ganglios linfáticos.

Abstract Introduction : Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population. Methods : The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients. Results : BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC. Conclusion : BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our popu lation. There is a significant correlation between BRAF mutation and lymph-node metastasis.

Research progress of CAR-T immunotherapy in solid tumors combined with new strategies / 中国药科大学学报

@#In recent years, the chimeric antigen receptor T-cell (CAR-T) therapy has achieved breakthrough progress in the treatment of hematologic malignancies. However, when it comes to solid tumors, numerous challenges persist.These include limited CAR-T cell infiltration, susceptibility to T cell exhaustion, off-target effects, and more.Thus, novel therapeutic strategies are imperative to enhance the efficacy of CAR-T therapy for solid tumors. In comparison to standalone CAR-T approaches, the combination of CAR-T with other tumor treatment modalities has demonstrated remarkable effectiveness in both preclinical and clinical research.This review article summarizes the advancements in combining CAR-T with various solid tumor treatments: antibody drugs, oncolytic viruses, tumor vaccines, and nanomedicines.The objective is to furnish a theoretical foundation and novel perspectives for the development of innovative CAR-T combination strategies tailored for solid tumor therapy.

Advances in application of regulatory T cells in transplant immune tolerance: from basic to clinical research / 器官移植

Regulatory T cells (Treg) are important inhibitory immune cells to establish immune tolerance, which play a pivotal role in regulating excessive immune response and autoimmune diseases of the host. Previous studies related to transplant immune tolerance have confirmed that increasing the number of Treg in vivo or enhancing the function of Treg serve as a therapeutic strategy to induce transplant immune tolerance. At present, Treg-based induction methods for transplant immune tolerance include adoptive infusion of Treg, in vivo amplification of Treg and utilization of antigen-specific Treg. In this article, the characteristics and mechanism of Treg, the latest research progress on basic experiments and clinical practice of Treg related to transplant immune tolerance at home and abroad were reviewed, and future challenges and development of Treg therapy were prospected, aiming to unravel the significance and application prospect of Treg in transplant immune tolerance, explore the advantages and limitations of Treg therapeutic strategies, and provide reference and evidence for subsequent research in this field.

Advances in Emerging Therapies for Multiple Myeloma / 肿瘤防治研究

Multiple myeloma (MM) is an incurable plasma cell malignancy with a typical course characterized by response to initial treatment and eventual resistance. Despite major advances in the clinical treatment of multiple myeloma driven by the introduction of new drugs (e.g., proteasome inhibitors and immunomodulators), MM remains incurable. Nevertheless, subsequent cycles of remission and relapse continue as long as new treatments are available to patients. With the development of many new treatments, the approval of 12 new drugs over the past 15 years, and the promising trend of clinical trials, the treatment landscape has dramatically changed and patient survival has improved. This article reviews the progress of new treatments for MM.

Research progress of synthetic biology-based CAR-T cell therapy for solid tumors / 中国肿瘤生物治疗杂志

@#[摘 要] 合成生物学借助工程化技术在人工生物系统的设计与构建方面已经取得了长足进展，尤其在CAR-T细胞的开发和应用中为实体肿瘤治疗带来了深刻变革。在合成生物学技术的支持下，新一代的CAR-T细胞可以在靶向肿瘤后激活细胞因子释放通路，实现CAR-T细胞在肿瘤部位的自我调节；工程化的T细胞在CAR的基础上也可以表达其他受体元件（如正交型IL-2、IL-9受体等），通过人工给药干预可在体内实现多功效、特异性刺激，这对于实现CAR-T细胞在体内的精准刺激和克服抑制性肿瘤微环境等意义非凡。此外，智能化CAR回路系统如synNotch基因回路系统和CAR开关系统等研究结果表明，CAR-T细胞可以通过自身基因回路的反馈或人工给药干预来发挥或终止杀伤功能，可有效保证CAR-T细胞在治疗过程中的安全性。虽然针对实体肿瘤靶点难题的CAR-T细胞开发目前尚未有突破性进展，但对于有明确靶点的肿瘤，Ⅰ期临床试验结果已经显示CAR-T细胞治疗实体肿瘤具有巨大潜力。因此，明确当下CAR-T细胞治疗实体肿瘤的作用机制和应用现状，可以对后续开发高效低毒CAR-T细胞提供新思路。

Advances in the study of the function of CD4+ CAR-T cell subsets in tumor therapy / 中国肿瘤生物治疗杂志

@#[摘 要] 嵌合抗原受体T（CAR-T）细胞疗法是目前治疗癌症最有效的一种免疫治疗方法，但CAR-T细胞功能障碍很大程度限制其自身对癌症治疗的效果。T细胞功能的差异以及记忆和效应T细胞的作用被证明在CAR-T细胞治疗中极为重要。CD8+ T细胞作为发挥抗癌作用的主要效应细胞一直是研究焦点，而对CD4+ T细胞的关注较少。CD4+ T细胞不仅可以通过激活CD8+ T细胞使其杀伤肿瘤细胞，还可以独立发挥抗肿瘤作用。现有研究发现，细胞因子、共刺激域和细胞代谢等因素均可影响CD4+ CAR-T细胞亚群的增殖和分化。本文主要综述了CD4+ CAR-T细胞亚群在治疗肿瘤中的重要性以及影响其增殖分化因素的研究进展，为进一步研发高效的CAR-T细胞提供新思路。

Construction and functional identification of CD19-CAR vector based on PiggyBac transposable system / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：开发基于PiggyBac（PB）转座系统的电转染CAR-T细胞制备方法并鉴定其体外抗肿瘤功能。方法：采用健康人外周血单个核细胞（PBMC）制备T细胞，通过分子克隆技术将CD19基因克隆到PB质粒（转座子）中后经电转染法将转座子和转座酶质粒导入激活的T细胞中，并测定其转染效率，最后运用流式细胞术及荧光素酶发光实验评估其对人Burkitt's淋巴瘤Raji细胞的杀伤能力。结果：电转染制备的CD19 CAR-T细胞转染效率较高（>60%），呈剂量依赖性，且CAR-T细胞相对于Pan-T细胞对Raji细胞杀伤能力显著（P<0.05）。结论：开发的PB转座系统的电转染方法可行，在体外对肿瘤细胞具有显著的杀伤能力，具备临床运用于CD19 CAR-T细胞制备的潜力。

Establishment and observation of a mouse model of IL-12-CAR-T cell-induced cytokine release syndrome / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：通过构建表达IL-12的小鼠CAR-T细胞，探讨经尾静脉将其输注于小鼠体内建立细胞因子释放综合征（CRS）模型的方法。方法：构建基于靶向鼠源CD19的CAR分子，包装逆转录病毒载体并感染小鼠T细胞构建mCD19-CAR-T、mCD19/IL-12-CAR-T细胞。通过构建小鼠体内胰腺癌Panc02-CD19细胞移植瘤模型，检测mCD19/IL-12-CAR-T细胞的抗肿瘤活性，ELISA法检测两种CAR-T细胞IL-12和IFN-γ分泌水平；经小鼠尾静脉输注mCD19/IL-12-CAR-T 细胞构建CAR-T细胞CRS小鼠模型，流式细胞术检测小鼠血清中IL-6、MCP-1、IL-1、IL-10、TNF-α、IFN-γ等细胞因子的含量，H-E染色法观察荷瘤小鼠肝、脾、肺和肾的病理组织学变化。结果：经过培养扩增的mCD19/IL-12-CAR-T细胞能有效分泌IL-12，CAR阳性率达（56.9±5.4）%；与非靶细胞Panc02或靶细胞Panc02-CD19共培养时，均能高分泌IFN-γ。成功构建小鼠胰腺癌Panc02-CD19细胞移植瘤模型，经小鼠尾静脉注射1×106个mCD19/IL-12-CAR-T细胞能显著抑制移植瘤的生长，但未能诱发严重CRS；输注2×106个mCD19/IL-12-CAR-T细胞后，小鼠出现体质量减轻、血清炎性因子水平升高、组织损伤，最终导致死亡等一系列典型CRS表现。结论：成功构建IL-12-CAR-T细胞诱发的小鼠CRS模型，其稳定性好、重复性高，具有广泛的应用前景。

Universal chimeric Fcγ receptor T cells with appropriate affinity for IgG1 antibody exhibit optimal antitumor efficacy

Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR-T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.

Slum compassionate community: expanding access to palliative care in Brazil / Comunidad de favela compasiva: ampliar el acceso a los cuidados paliativos en Brasil / Comunidade compassiva de favela: ampliando o acesso aos cuidados paliativos no Brasil

ABSTRACT Objective: To describe the implementation of a compassionate community in Rocinha and Vidigal slums, located in the city of Rio de Janeiro. Method: Report on the experience of implementing a Compassionate Community based on the World Health Organization conceptual bases, supported by university extension guidelines. Results: Initially, local leaders and residents were recruited and trained in palliative care. Subsequently, health professionals from different specialties engaged in the project through volunteering. Home visits were instituted in the form of interconsultation and "sponsorships" by residents and health professionals to people in palliative care and family members. Finally, the health care network in the territory was integrated in order to recognize the project as a support network. Conclusion: We highlight the experience as living work in health, which involves relationships and creative processes, which mobilize structured technical knowledge and relationships between people and soft-hard and soft technologies, making it possible to recognize powers in the territory.

RESUMEN Objetivo: Describir la implementación de una comunidad compasiva en las favelas de Rocinha y Vidigal, ubicadas en la ciudad de Río de Janeiro. Método: Relato de la experiencia de implementación de una Comunidad Compasiva a partir de las bases conceptuales de la Organización Mundial de la Salud, sustentada en lineamientos de extensión universitaria. Resultados: Inicialmente, se reclutaron y capacitaron a líderes locales y residentes en cuidados paliativos. Posteriormente, profesionales de la salud de diferentes especialidades se involucraron en el proyecto a través del voluntariado. Se instituyeron visitas domiciliarias en la modalidad de interconsulta y "patrocinios" por parte de residentes y profesionales de salud a personas en cuidados paliativos y familiares. Finalmente, se integró la Red de Atención a la Salud del territorio para reconocer el proyecto como una red de apoyo. Conclusión: Destacamos la experiencia como trabajo vivo en salud, que involucra relaciones y procesos creativos, que movilizan saberes técnicos estructurados y relaciones entre personas y tecnologías ligeras-duras y ligeras, posibilitando el reconocimiento de poderes en el territorio.

RESUMO Objetivo: Descrever a implementação de uma comunidade compassiva nas favelas da Rocinha e Vidigal, localizadas na cidade do Rio de Janeiro. Método: Relato da experiência da implementação de uma Comunidade Compassiva a partir das bases conceituais da Organização Mundial da Saúde, amparada pelas diretrizes da extensão universitária. Resultados: Inicialmente, lideranças locais e moradores foram recrutados e receberam treinamento sobre cuidados paliativos. Posteriormente, profissionais de saúde de diferentes especialidades engajaram-se no projeto por meio da prática do voluntariado. Foram instituídas visitas domiciliares na modalidade interconsulta e "apadrinhamentos" por moradores e profissionais de saúde às pessoas em cuidados paliativos e familiares. Por fim, a Rede de Atenção à Saúde do território foi integrada de forma a reconhecer o projeto como rede de apoio. Conclusão: Destacamos a experiência como trabalho vivo em saúde, que envolve relações e processos criativos, os quais mobilizam o saber técnico estruturado e as relações entre as pessoas e as tecnologias leve-duras e leves, tornando factível o reconhecimento de potências no território.

Migrant women caregivers' experiences in end-of-life formal care / Experiências de mulheres migrantes cuidadoras em cuidados formais no final da vida / Experiencias de cuidadoras migrantes en el cuidado formal al final de la vida

ABSTRACT Objective: To describe and understand the experience of Latin American migrant women as caregivers of elderly people in situations of advanced illness and end of life. Method: Qualitative study using Gadamer's hermeneutic phenomenology. Data were collected in 2019 through 9 semi-structured interviews with Latin American women caregivers, who had cared for people at the end of life, in the Province of Granada (Spain). Results: Two themes emerged: "Migrant caregiver at the end of life" and "And now, what should I do?": the impact of the loss at the economic, emotional and labor level Conclusion: Care during the end of life of the cared person generates an additional overload to the situation of migrant women. The experience of this stage is related to the bond with the persons cared and their families, which may affect the development of complicated grief and personal problems related to the loss of employment and the absence of economic support.

RESUMO Objetivo: Descrever e compreender a experiência de mulheres migrantes latino-americanas, cuidadoras de idosos em situações de doença avançada e de fim da vida. Método: Estudo qualitativo baseado na fenomenologia hermenêutica de Gadamer. Os dados foram coletados em 2019 por meio de 9 entrevistas semiestruturadas com mulheres cuidadoras latino-americanas que cuidaram de pessoas no final da vida em Granada (Espanha). Resultados: Surgiram dois temas: "Cuidador migrante no fim da vida" e "E agora, o que eu faço?": o impacto da perda nos níveis econômico, emocional e de trabalho. Conclusão: O cuidado durante o fim da vida da pessoa cuidada gera uma sobrecarga adicional à situação das mulheres migrantes. A experiência dessa fase está relacionada ao vínculo com a pessoa cuidada e sua família, o que pode ter um impacto na elaboração de luto complicado e problemas pessoais relacionados à perda do emprego e à ausência de apoio econômico.

RESUMEN Objetivo: Describir y comprender la experiencia de las mujeres migrantes latinoamericanas como cuidadoras de personas mayores en situación de enfermedad avanzada y final de la vida. Método: Estudio cualitativo desde la fenomenología hermenéutica de Gadamer. Los datos fueron recogidos en 2019 mediante 9 entrevistas semiestructuradas a cuidadoras latinoamericanas, que hubieran atendido a personas al final de la vida en Granada (España). Resultados: Surgieron 2 temas: "Cuidadora migrante al final de la vida" e "Y ahora ¿qué hago?": El impacto de la pérdida a nivel económico, emocional y laboral. Conclusión: La atención durante el final de la vida de la persona cuidada genera una sobrecarga adicional a la situación de las mujeres migrantes. La vivencia de esta etapa se relaciona con el vínculo con la persona cuidada y su familia, que puede incidir en la elaboración de un duelo complicado y problemas personales relacionados con la pérdida de empleo y la ausencia de apoyo económico.

Monitoreo de las insuficiencias orgánicas en pacientes graves con hemopatías malignas por el uso de las células CAR-T / Monitoring of organ failures in critically ill patients with blood malignancies by the use of CAR - T cell

Introducción: La inmunoterapia con células T modificadas con receptor quimérico antígeno específico es un tratamiento prometedor para hemopatías malignas. Sin embargo, la activación dirigida de la respuesta inmunitaria desata en ciertos casos complicaciones específicas graves y mortales. Objetivos: Describir el monitoreo de las complicaciones por el uso de las células T con receptor antígeno quimérico en pacientes graves con hemopatías malignas. Métodos: Se realizó una investigación bibliográfico documental acerca del tema. Se consultaron las bases de datos de SciELO y PubMed de los últimos cinco años. Conclusiones: Se describieron las complicaciones derivadas de la terapia con células inmunoefectoras, que aumentan el desarrollo de insuficiencias orgánicas, a través del síndrome de liberación de citoquinas y el síndrome de toxicidad neurológica. El tratamiento se basó en establecer medidas de monitorización y soporte, tratamiento con anticonvulsivantes, corticosteroides e ingreso en los servicios de medicina intensiva de forma precoz. Se disminuyó el riesgo en la aparición de complicaciones y muerte con un adecuado monitoreo de las insuficiencias orgánicas derivadas de la inmunoterapia de células T con receptor antígeno quimérico.

Introduction: Immunotherapy with T-cells modified with antigen-specific chimeric receptor is a promising treatment for malignant hemopathies. However, the targeted activation of the immune response in certain cases unleashes specific severe and fatal complications. Objectives: To describe the monitoring of complications from the use of CAR T-cells in critically ill patients with blood malignancies. Methods: A bibliographical-documentary research on the subject was carried out. The SciELO and Pubmed databases of the last five years were consulted. Conclusions: Complications derived from the therapy with immunoeffector cells are described, which increase the development of organ failures, through the cytokine release syndrome and the neurological toxicity syndrome. Treatment is based on monitoring and support measures, treatment with anticonvulsants, corticosteroids, and early admission to intensive care. With adequate monitoring of organ failure derived from chimeric antigen receptor T-cell immunotherapy, a decreased risk of complications and death in these patients was carried out.

CAR-T cell therapy for multiple myeloma: a practical toolkit for treatment in Brazil

ABSTRACT Introduction Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success. Methods A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions. Results This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers. Conclusion We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil.

Adolescent mothers, self-care and childcare: content validation of an Event History Calendar / Madres adolescentes, autocuidado y cuidado de los hijos: validación del contenido de un calendario histórico de acontecimientos / Mães adolescentes, autocuidado e cuidado infantil: validação de conteúdo de um calendário histórico de eventos

ABSTRACT Objective: To validate the content of the tool Event History Calendar Adolescent Mother: strengthening self-care and child care. Method: Methodological study using the Delphi technique, conducted in two rounds, involving 37 nursing specialists. In data collection, from December/2019 to August/2020, a semi-structured questionnaire composed of 47 items related to the two dimensions of the tool: Self-care and Child Care was used. The Content Validity Index ≥ 0.80 was used to assess agreement among the experts. Qualitative elements were analyzed for clarity and comprehensiveness of content. Results: In the first round, 46 items showed Content Validity Index ≥ 0.80. The qualitative elements pointed out more clarity for the adolescent audience. After the changes, the tool presented 30 items. In the second round, the 30 items evaluated achieved Content Validity Index ≥ 0.80. The qualitative considerations were translated into modifications in the content and sequence in the final version of the tool. Conclusion: The validated tool obtained adequate evaluation of the items of each dimension, related to adolescent mother self-care and child care, with a high degree of comprehensibility.

RESUMEN Objetivo: Validar el contenido de la herramienta Event History Calendar Madre Adolescente: fortaleciendo el autocuidado y el cuidado de los hijos. Método: Estudio metodológico mediante la técnica Delphi, realizado en dos rondas, en el que participaron 37 expertos en enfermería. En la recopilación de datos, de diciembre de 2019 a agosto de 2020, se utilizó un cuestionario semiestructurado compuesto por 47 ítems relacionados con dos dimensiones de la herramienta: Autocuidado y Cuidado del niño. Se utilizó el Índice de Validez del Contenido ≥ 0,80 para evaluar el acuerdo entre los expertos. Se analizaron los elementos cualitativos para comprobar la claridad y exhaustividad del contenido. Resultados: En la primera ronda, 46 ítems presentaron Índice de Validez de Contenido ≥ 0,80. Los elementos cualitativos apuntan a la necesidad de una mayor claridad para el público adolescente. Tras los cambios, la herramienta presentaba 30 ítems. En la segunda ronda, los 30 ítems evaluados alcanzaron un Índice de Validez de Contenido ≥ 0,80. Las consideraciones cualitativas se tradujeron en modificaciones del contenido y la secuencia en la versión final de la herramienta. Conclusión: El instrumento validado obtuvo evaluación adecuada de los ítems de cada dimensión, relacionados al autocuidado de la madre adolescente y al cuidado del niño, con alto grado de comprensibilidad.

RESUMO Objetivo: Validar o conteúdo da ferramenta Event History Calendar Mãe Adolescente: fortalecendo o autocuidado e o cuidado da criança. Método: Estudo metodológico com a técnica Delphi, realizado em duas rodadas, envolvendo 37 especialistas de enfermagem. Na coleta de dados, de dezembro/2019 a agosto/2020, foi utilizado um questionário semiestruturado composto por 47 itens relacionados às duas dimensões da ferramenta: Autocuidado e Cuidado da criança. O Índice de Validade de Conteúdo ≥ 0,80 foi utilizado para avaliar a concordância entre os especialistas. Elementos qualitativos foram analisados quanto à clareza e abrangência do conteúdo. Resultados: Na primeira rodada, 46 itens apresentaram Índice de Validade de Conteúdo ≥ 0,80. Os elementos qualitativos apontaram necessidade de maior clareza para o público adolescente. Após as alterações, a ferramenta apresentou 30 itens. Na segunda rodada, os 30 itens avaliados alcançaram Índice de Validade de Conteúdo ≥ 0,80. As considerações qualitativas foram traduzidas em modificações no conteúdo e sequência na versão final da ferramenta. Conclusão: A ferramenta validada obteve avaliação adequada dos itens de cada dimensão, relacionados ao autocuidado da mãe adolescente e cuidado da criança, com alto grau de compreensibilidade.

Relationship of cytokines to adverse reaction of chimeric antigen receptor T cell immunotherapy and targeted drug intervention / 中国生物制品学杂志

@#Chimeric antigen receptor T cell(CAR-T)immunotherapy is the most potential adoptive immunotherapy for malignant tumors,which needs no antigen presenting cells(APC)and is not limited by major histocompatibiliy complex(MHC). CAR-T immunotherapy not only recognizes and kills tumor cells directly,but also forms memory T cells and establishs long-term anti-tumor mechanism,of which the effect in leukemia,multiple myeloma and other non-solid tumors as well as the great potential in solid tumors have been widely verified. However,a variety of adverse reactions such as cytokine release syndrome(CRS),neurotoxicity(NT)and miss target effect are produced during CAR-T immunotherapy,of which the occurrence of CRS and NT may be related to the abnormal level of cytokines. Remarkable increase of cytokine level is a major characteristics of CRS. However,the increase of cytokines is neither the root cause nor the only result of CAR-T adverse reaction. CAR-T immunotherapy has a high incidence of adverse reaction which may even endanger the life of patients. Cytokine targeted drugs such as Anakinra and Tocilizumab may decrease the incidence of adverse reaction and improve the prognosis of patients. This paper reviews the correlation of cytokines with CRS and NT in CAR-T immunotherapy and the effect of cytokine targeting drugs,so as to provide a reference for the basic research,quality control and clinical application of CAR-T immunotherapy.

Research progress of chimeric antigen receptor T cell and T cell antigen coupler modified T cell technology / 中国生物制品学杂志

@#At present,malignant tumor has become one of the public problems that seriously threaten human health. In addition to surgery,radiotherapy,chemotherapy,targeted therapy and other methods,with the development of molecular biology,immunotherapy has also developed rapidly,becoming an emerging method of cancer treatment. The most commonly used immune cells in clinical treatment are DC,NK,CIK,CTL and chimeric antigen receptor T cell(CAR-T). Among them,CAR-T technology is the initial technology for global research,while due to its off-target,neurotoxicity,transfection vector defects and other problems,it also has certain limitations in clinical application. T cell antigen coupler modified T cell(TAC-T)technology is a new technology developed on the basis of CAR-T,which uses natural T cell receptor(TCR)to modify T cells and retarget the antigen of cancer cells. In this paper,the research status of CAR-T technology and the research progress of TAC-T technology are reviewed in order to provide reference for further study on the mechanism of TAC-T technology and its safety of clinical application.

Development strategy and clinical research progress of universal chimeric antigen receptor T-cell drugs / 中国药科大学学报

@#Chimeric antigen receptor T-cell (CAR-T) immunotherapy has made a breakthrough in the clinical treatment of a variety of hematological tumors.However, the CAR-T cell products listed at China and abroad are all autologous CAR-T.Compared with autologous CAR-T treatment, universal CAR-T exhibits significant advantages, which could fulfill the treatment demand of more patients, but also displays high technical barriers.This paper reviews the universal CAR-T, clearly points out the two major challenges faced by the development of universal CAR-T, and then summarizes and analyzes the feasible solutions according to the mechanism causing the two major problems.This paper also summarizes domestic and foreign companies producing universal CAR-T and the latest clinical progress of their superior products, and then discusses the feasibility of the development strategy from another aspect, in order to provide ideas for developing a new generation of universal CAR-T cell therapy products.

Genome editing in cancer biotherapy: strategies, challenges and future directions / 中国肿瘤生物治疗杂志

@#[摘 要] CRISPR等基因编辑技术在多学科、多领域产生了革命性影响，也极大地推动了肿瘤生物治疗研究方法的转变和治疗新策略的形成。在肿瘤研究中，基因编辑加速了肿瘤细胞和免疫细胞中生物治疗新靶点的发现，推动了癌基因、抑癌基因、表观分子、耐药基因等“肿瘤细胞正常化”靶向编辑新策略的提出，促进了CAR-T、TCR-T细胞等过继细胞治疗方法向“通用型”、“即用型”的迭代，也极大地加速了CAR-T细胞等细胞治疗的临床应用。通过更加精准基因编辑系统的研发、基因递送策略的不断进步，以及多靶点编辑、定点插入和体内时空可控编辑的发展，将进一步降低基因编辑的脱靶效应，提高疗效和安全性，同时控制成本，推动基因编辑在肿瘤生物治疗中更加广泛的应用，且有望在实体瘤治疗方面实现新的突破。

Progress of Chimeric Antigen Receptor Gene Modified-T Cell Immunotherapy for Thoracic Malignancies / 肿瘤防治研究

With a deepened understanding of the pathophysiology and pathogenesis of thoracic malignancies, the treatment has been transited from traditional treatment on the basis of surgery, radiotherapy, and chemotherapy to individualized and precise targeted therapy and immunotherapy. As an antitumor immunotherapy, chimeric antigen receptor gene-modified T (CAR-T) cells have been approved by the FDA for the treatment of hematological malignancies in five CAR-T products. They have also achieved good therapeutic effects in solid tumors. However, significant challenges remain in the clinical application of CAR-T cell immunotherapy in thoracic malignancies. In this review, the latest research progress of CAR-T cell immunotherapy in the treatment of thoracic malignancies were summarized, including the basic characteristics of CAR-T cells, the popular target antigens, and the existing problems and challenges, to provide new ideas and strategies for clinical immunotherapy of thoracic malignancies.

Advance in chimeric antigen receptor-T cell immunotherapy for multiple myeloma / 中国生物制品学杂志

@#In recent years,considerable progress has been made in the treatment of multiple myeloma(MM).However,despite the current improved prognosis of this malignancy,it always ends in relapse and therefore new therapeutic approaches are urgently needed to overcome it.The chimeric antigen receptor(CAR)-T cells targeting B cell maturation antigen(BCMA),cluster of differentiation 19(CD19),cluster of differentiation 38(CD38) and kappa light chains have been evaluated,and have achieved remarkable results in clinical trials.However,even when MM is treated with CAR-T cell therapy,most patients eventually relapse,which is the greatest limitation of this therapy.This paperreviewedthe research progress,limitations and optimization of CAR-T cell immunotherapy in the treatment of MM.