The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity.
Nat Commun
; 9(1): 3049, 2018 08 03.
Article
em En
| MEDLINE
| ID: mdl-30076299
ABSTRACT
Engineering T cells with chimeric antigen receptors (CARs) is an effective method for directing T cells to attack tumors, but may cause adverse side effects such as the potentially lethal cytokine release syndrome. Here the authors show that the T cell antigen coupler (TAC), a chimeric receptor that co-opts the endogenous TCR, induces more efficient anti-tumor responses and reduced toxicity when compared with past-generation CARs. TAC-engineered T cells induce robust and antigen-specific cytokine production and cytotoxicity in vitro, and strong anti-tumor activity in a variety of xenograft models including solid and liquid tumors. In a solid tumor model, TAC-T cells outperform CD28-based CAR-T cells with increased anti-tumor efficacy, reduced toxicity, and faster tumor infiltration. Intratumoral TAC-T cells are enriched for Ki-67+ CD8+ T cells, demonstrating local expansion. These results indicate that TAC-T cells may have a superior therapeutic index relative to CAR-T cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes
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Receptores de Antígenos
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Linfócitos T
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Especificidade do Receptor de Antígeno de Linfócitos T
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Receptores de Antígenos Quiméricos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article