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Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response.
Nat Commun ; 10(1): 2087, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064990
ABSTRACT
T cells expressing CD19-targeting chimeric antigen receptors (CARs) reveal high efficacy in the treatment of B cell malignancies. Here, we report that T cell receptor fusion constructs (TRuCs) comprising an antibody-based binding domain fused to T cell receptor (TCR) subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens. Unlike CARs, TRuCs become a functional component of the TCR complex. TRuC-T cells kill tumor cells as potently as second-generation CAR-T cells, but at significant lower cytokine release and despite the absence of an extra co-stimulatory domain. TRuC-T cells demonstrate potent anti-tumor activity in both liquid and solid tumor xenograft models. In several models, TRuC-T cells are more efficacious than respective CAR-T cells. TRuC-T cells are shown to engage the signaling capacity of the entire TCR complex in an HLA-independent manner.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Receptores de Antígenos de Linfócitos T / Linfócitos T / Imunoterapia Adotiva / Anticorpos de Cadeia Única / Receptores Artificiais / Neoplasias Limite: Animais / Feminino / Humanos Idioma: Inglês Revista: Nat Commun Assunto da revista: Biologia / Ciência Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Estados Unidos