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Abstract：
Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70- targeted allogeneic CAR T cells. Significance: Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.
摘要：
透明细胞肾细胞癌（ccRCC）的治疗方法仍然有限；然而，嵌合抗原受体(CAR)T细胞疗法可能提供新的治疗选择.CTX130，一种同种异体CD70靶向CAR-T细胞产物，被开发用于治疗晚期或难治性ccRCC。我们报告CTX130显示出良好的临床前增殖和细胞毒性谱，并且完全消退了RCC异种移植肿瘤。我们还报告了16例复发/难治性ccRCC患者在I期接受CTX130的结果，多中心，首次人体临床试验。没有患者遇到剂量限制性毒性，81.3%的患者实现了疾病控制。一名患者在3年时保持持久的完全反应。最后,我们报告了下一代CAR-T结构，CTX131，其中对CTX130的协同效力编辑在临床前研究中赋予改善的扩增和功效。这些数据代表了用CD70靶向的同种异体CART细胞治疗ccRCC和其他CD70+恶性肿瘤的概念证明。
■尽管CAR-T细胞在血液系统恶性肿瘤中的作用已经确立，实体肿瘤的临床经验令人失望。这项临床试验证明了RCC患者的首次完全反应，增强CART细胞在实体瘤治疗中的潜在益处。
■尽管CAR-T细胞在血液系统恶性肿瘤中的作用已经确立，实体肿瘤的临床经验令人失望。这项临床试验证明了RCC患者的首次完全反应，增强CART细胞在实体瘤治疗中的潜在益处。
