RESUMO
MUC1 is a shared tumor antigen expressed on >80% of human cancers. We completed the first prophylactic cancer vaccine clinical trial based on a non-viral antigen, MUC1, in healthy individuals at-risk for colon cancer. This trial provided a unique source of potentially effective and safe immunotherapeutic drugs, fully-human antibodies affinity-matured in a healthy host to a tumor antigen. We purified, cloned, and characterized 13 IgGs specific for several tumor-associated MUC1 epitopes with a wide range of binding affinities. These antibodies bind hypoglycosylated MUC1 on human cancer cell lines and tumor tissues but show no reactivity against fully-glycosylated MUC1 on normal cells and tissues. We found that several antibodies activate complement-mediated cytotoxicity and that T cells carrying chimeric antigen receptors with the antibody variable regions kill MUC1(+) target cells, express activation markers, and produce interferon gamma. Fully-human and tumor-specific, these antibodies are candidates for further testing and development as immunotherapeutic drugs.
Assuntos
Anticorpos/imunologia , Neoplasias da Mama/imunologia , Vacinas Anticâncer/imunologia , Mucina-1/imunologia , Adulto , Sequência de Aminoácidos , Afinidade de Anticorpos/imunologia , Sequência de Bases , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Vacinas Anticâncer/uso terapêutico , Linhagem Celular , Linhagem Celular Tumoral , Citotoxicidade Imunológica/imunologia , Epitopos/imunologia , Feminino , Células HEK293 , Humanos , Imunoglobulina G/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Células MCF-7 , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto JovemRESUMO
The site-specific modification of proteins with fluorophores can render a protein fluorescent without compromising its function. To avoid self-quenching from multiple fluorophores installed in close proximity, we used Holliday junctions to label proteins site-specifically. Holliday junctions enable modification with multiple fluorophores at reasonably precise spacing. We designed a Holliday junction with three of its four arms modified with a fluorophore of choice and the remaining arm equipped with a dibenzocyclooctyne substituent to render it reactive with an azide-modified fluorescent single-domain antibody fragment or an intact immunoglobulin produced in a sortase-catalyzed reaction. These fluorescent Holliday junctions improve fluorescence yields for both single-domain and full-sized antibodies without deleterious effects on antigen binding.
Assuntos
Alcinos/química , Anticorpos/análise , Anticorpos/química , Azidas/química , DNA Cruciforme/química , Corantes Fluorescentes/químicaRESUMO
The authors explain what cryotherapy is, the pathologies for which this therapy is employed and the various manners medical professionals may apply this therapy. The authors mention the results of different research studies found on the internet.
Assuntos
Crioterapia , Pesquisa Biomédica , Crioterapia/métodos , HumanosRESUMO
Se explica qué es la crioterapia, las patologías donde se utiliza y las distintas formas de aplicación por parte de los profesionales de la salud. Se difunden los resultados de diferentes estudios de investigación en la red (AU)
Assuntos
Humanos , Cuidados de Enfermagem/métodos , Crioterapia/enfermagem , Crioterapia/efeitos adversos , Crioterapia , Verrugas/terapia , Papiloma/terapia , Traumatismos em Atletas/terapia , Condiloma Acuminado/terapia , Temperatura Baixa/efeitos adversos , Crioterapia/métodos , Neoplasias da Próstata/terapiaRESUMO
Partindo de um breve esboço histórico da psicanálise de crianças, procuramos, neste ensaio, identificar os pressupostos filosóficos que estiveram na base das divergências teóricas presentes na controvérsia que envolveu a clínica psicanalítica na infância, de forma a explicitar a estreita inter-relação entre o desenvolvimento dos conceitos epistemológicos e os diferentes efeitos desta démarche sobre a investigação psicanalítica, concluindo com uma formulação que, pretendemos, possa refletir a tendência predominante na prática psicanalítica com crianças, hoje(AU)
