决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.
过继性 T 细胞转移疗法(ACT)显著推动了肿瘤免疫治疗的进展。
过继T细胞转移疗法(ACT)显著推动了肿瘤免疫治疗发展。在多种靶向实体瘤的策略中,T细胞受体工程化T细胞(TCR-T)疗法已成为极具前景的方法,可适用于更广泛患者群体;在某些实体恶性肿瘤中,其肿瘤杀伤活性优于CAR-T(CAR-T)及肿瘤浸润T细胞/淋巴细胞(TIL)疗法。然而,TCR-T临床疗效仍受限制。本文介绍TCR-T治疗实体瘤面临的局限和挑战,总结克服这些局限及推动其临床应用的近期工作,并分析其当前临床应用状态及实体瘤患者中的疗效。我们预期,依托高亲和力TCR、丰富多样的靶抗原、协同多模式治疗策略及高效体外生产流程,TCR-T精准治疗将使更广泛患者群体获益,并展现新的临床应用潜力。
Adoptive T-cell transfer therapy (ACT) has significantly propelled the advancement of tumor immunotherapy. Among various strategies targeting solid tumors, the T-cell receptor (TCR)-engineered T-cell (TCR-T cell) therapy has emerged as a highly promising approach, exhibiting an expanded therapeutic window across diverse patient populations and superior tumoricidal activity in certain solid malignancies compared with chimeric antigen receptor T cell (CAR-T) and tumor-infiltrating T cells/lymphocyte (TIL) therapies. However, its clinical efficacy remains constrained. In this paper, we introduce the limitations and challenges faced by TCR-T cells in solid tumor treatment, and summarize recent efforts overcoming these limitations and translating TCR-T cell therapies into clinical application. Furthermore, their current status and effectiveness in clinical solid tumor patients were analyzed. We expect that the precision therapies of TCR-T cells, with the support of high-affinity TCRs and a diverse array of target antigens, multimodal synergistic therapy strategies and efficient in vitro production processes, will benefit a wider patient population, thus revealing new clinical application potential.
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