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High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells / 医学前沿
Frontiers of Medicine ; (4): 69-82, 2019.
Artigo em Inglês | WPRIM | ID: wpr-771259
ABSTRACT
Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1 HLA-A*0201-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-γ and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Ativação Linfocitária / Receptores de Antígenos de Linfócitos T / Linfócitos T / Engenharia Genética / Antígeno HLA-A2 / Citocinas / Imunoterapia Adotiva / Citotoxicidade Imunológica / Linhagem Celular Tumoral / Alergia e Imunologia Limite: Humanos Idioma: Inglês Revista: Frontiers of Medicine Ano de publicação: 2019 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Ativação Linfocitária / Receptores de Antígenos de Linfócitos T / Linfócitos T / Engenharia Genética / Antígeno HLA-A2 / Citocinas / Imunoterapia Adotiva / Citotoxicidade Imunológica / Linhagem Celular Tumoral / Alergia e Imunologia Limite: Humanos Idioma: Inglês Revista: Frontiers of Medicine Ano de publicação: 2019 Tipo de documento: Artigo