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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.
Artículo en Inglés | 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.
Asunto(s)

Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Activación de Linfocitos / Receptores de Antígenos de Linfocitos T / Linfocitos T / Ingeniería Genética / Antígeno HLA-A2 / Citocinas / Inmunoterapia Adoptiva / Citotoxicidad Inmunológica / Línea Celular Tumoral / Alergia e Inmunología Límite: Humanos Idioma: Inglés Revista: Frontiers of Medicine Año: 2019 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Activación de Linfocitos / Receptores de Antígenos de Linfocitos T / Linfocitos T / Ingeniería Genética / Antígeno HLA-A2 / Citocinas / Inmunoterapia Adoptiva / Citotoxicidad Inmunológica / Línea Celular Tumoral / Alergia e Inmunología Límite: Humanos Idioma: Inglés Revista: Frontiers of Medicine Año: 2019 Tipo del documento: Artículo