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:Commentary on "Comparative efficacy and safety of PSCA CAR-engineered Vδ1 γδ T cells for immunotherapy of pancreatic cancer".
未经改造的 T 细胞过继转移临床获益有限,促使研究转向嵌合抗原受体(CAR)工程化,以增强激活、持久性和肿瘤特异性。
未修饰T细胞的过继转移临床获益有限,因此研究方向转向嵌合抗原受体(CAR)工程化,以增强细胞活化、持久性和肿瘤特异性。CAR技术使T细胞成为有前景的载体,因为T细胞具有类先天免疫细胞毒性,并能以不依赖HLA的方式识别靶标。CAR-T临床试验证据显示,CAR-T细胞输注后可持续存在数月至数年,提示其可能长期参与癌症免疫监视。在不同亚群中,Vγ9Vδ2 T细胞在外周血中占主导地位,因此过去优先用于CAR工程化。然而,近期进展已支持扩增Vδ1 T细胞;这类细胞具有组织驻留特性且较不易耗竭。在一项重要的比较研究中,Li等人在Vδ1、Vγ9Vδ2和常规T细胞中评估靶向PSCA的CAR,发现短期肿瘤控制效果相近,但转录和表型程序各不相同。这些结果凸显CAR-T疗法需针对不同细胞亚群进行优化。在着手解决实体瘤额外挑战之前,血液系统恶性肿瘤早期研究可提供实用的概念验证。在产业投资趋紧的背景下,这种聚焦式开发对推动CAR-T领域发展或许至关重要。
Adoptive transfer of unmodified T cells has shown limited clinical benefit, prompting a shift toward chimeric antigen receptor (CAR) engineering to enhance activation, persistence, and tumor specificity. CAR technology positions T cells as promising carriers due to their innate-like cytotoxicity and HLA-independent recognition. Evidence from CAR T-cell trials indicates that CAR T cells can persist for months to years post-infusion, suggesting their potential contribution to long-term immune surveillance against cancer. Among subsets, V 9V 2 T cells dominate peripheral blood and have been preferentially used for CAR engineering. Recent advances, however, enable the expansion of V 1 T cells, known for their tissue residency and resistance to exhaustion. In a key comparative study, Li et al benchmarked PSCA-targeted CARs in V 1, V 9V 2, and T cells, showing similar short-term tumor control but distinct transcriptional and phenotypic programs. These findings highlight the need for subset-specific optimization of CAR-T therapies. Early studies in hematologic malignancies could provide a practical proof of concept, before tackling the additional challenges of solid tumors. Such focused development may be essential to advance the CAR-T field amid tightening industry investment.
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