肿瘤细胞治疗研究
英文原题：PSCA CAR Vδ1 T cells: a safer off-the-shelf CAR T therapy for pancreatic cancer?
胰腺癌仍是最致命的恶性肿瘤之一，5 年生存率约为 13%。
胰腺癌仍是致死率最高的恶性肿瘤之一，5 年生存率约为 13%。嵌合抗原受体（CAR）T 细胞疗法带来希望，但常规 T 细胞可能引发严重毒性；用于异体治疗时还可能导致移植物抗宿主病（GvHD）。相比之下，γδ T 细胞识别肿瘤不受主要组织相容性复合体（MHC）限制，也不太可能引起 GvHD，因此适合作为“现货型”免疫疗法候选。Li 等人将靶向前列腺干细胞抗原（PSCA）的 CAR 导入 Vδ1 γδ T 细胞，并在胰腺癌临床前模型中将其与 CAR 修饰 Vδ2 T 细胞及常规 T 细胞进行比较。三组细胞的肿瘤杀伤效果相当，但 CAR Vδ1 T 细胞未引起 CAR 常规 T 细胞所见的 GvHD 或全身毒性。与 CAR Vδ2 细胞相比，其耗竭程度也更低，提示可能具有更强的持续性。Vδ1 CAR-T 细胞可在体外有效扩增，冻存后仍保持较强效力，这是实现“现货型”产品的重要要求。这些发现提示 CAR Vδ1 T 细胞可能是传统 CAR-T 细胞更安全的替代选择。未来仍需开展严格的临床评估，以确认这一策略在患者中的安全性和疗效是否更优。
Pancreatic cancer remains among the deadliest malignancies, with a 5-year survival of ~13%. Chimeric antigen receptor (CAR) T -cell therapy offers hope, but conventional T cells can trigger severe toxicities, including graft-versus-host disease (GvHD) when used for allogeneic therapy. By contrast, T cells recognize tumors without MHCmajor histocompatibility complex restriction and are unlikely to cause GvHD, making them attractive candidates for "off-the-shelf" immunotherapy. Li et al engineered the V 1 subset of T cells with a CAR targeting prostate stem cell antigen (PSCA) and compared these cells to CAR-engineered V 2 and conventional T cells in preclinical pancreatic cancer models. All three groups showed comparable tumor killing efficacy, but the CAR V 1 T cells induced none of the GvHD or systemic toxicity seen with CAR T cells. They also displayed lower exhaustion than CAR V 2 cells, suggesting potential for greater persistence. V 1 CAR T cells could be expanded robustly ex vivo and remained highly potent even after cryopreservation, a key "off-the-shelf" requirement. These findings position CAR V 1 T cells as a safer alternative to traditional CAR T cells. Future rigorous clinical evaluation will be needed to confirm superior safety and efficacy of this promising approach in patients.
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