Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cancer Control. 2013 Oct;20(4):289-97. doi: 10.1177/107327481302000406.
Current FDA-approved therapeutic options for patients with metastatic melanoma include dacarbazine, interleukin 2, ipilimumab, vemurafenib, dabrafenib, and trametinib, but long-term tumor regression using available agents remains out of reach for most patients. Adoptive cell transfer (ACT) with autologous tumor-infiltrating lymphocytes (TILs) has shown encouraging results in clinical trials, with evidence of durable ongoing complete responses in patients with advanced melanoma. Emerging techniques to engineer T-cell receptors (TCRs) or chimeric antigen receptors (CARs) using lymphocytes from peripheral blood may offer new tactics in ACT.
We reviewed the literature to provide a synopsis on the development and clinical trial results of ACT, as well as the future outlook for using ACT in patients with metastatic melanoma.
ACT with TILs as part of a lymphodepleting regimen has been shown in clinical trials to cause objective clinical responses in approximately 40% to 72% of patients with metastatic melanoma, with up to 40% of those patients experiencing complete responses lasting up to 7 years ongoing. Pilot trials using TCR-engineered cells against melanoma-associated antigens MART-1 and gp100 and the cancer-testis antigen NY-ESO-1 have shown clinical responses in patients with melanoma. CAR cells directed against melanoma have been tested only in preclinical models; however, CAR cells targeting other histologies such as lymphoma have elicited antitumor responses in patients.
An example of state-of-the-art personalized medicine, ACT is a potentially curative therapy for patients with metastatic melanoma. Ongoing trials aiming to simplify the regimens may allow a broader range of patients to be treated and enable ACT to be offered by academic cancer centers.
目前，美国食品和药物管理局（FDA）批准的转移性黑色素瘤治疗选择包括达卡巴嗪、白细胞介素 2、易普利姆玛、维莫非尼、达拉非尼和曲美替尼，但大多数患者仍无法通过现有药物实现长期肿瘤消退。过继细胞转移（ACT）联合自体肿瘤浸润淋巴细胞（TIL）在临床试验中取得了令人鼓舞的结果，证据表明晚期黑色素瘤患者存在持久的完全缓解。利用外周血淋巴细胞构建 T 细胞受体（TCR）或嵌合抗原受体（CAR）的新兴技术可能为 ACT 提供新策略。
我们查阅文献，对 ACT 的发展和临床试验结果以及 ACT 在转移性黑色素瘤患者中的未来前景进行综述。
临床试验表明，作为淋巴细胞耗竭方案的一部分，TIL 的 ACT 可使约 40%至 72%的转移性黑色素瘤患者产生客观的临床反应，其中多达 40%的患者出现持续长达 7 年的完全缓解。针对黑色素瘤相关抗原 MART-1 和 gp100 以及癌症睾丸抗原 NY-ESO-1 的 TCR 工程细胞和针对黑色素瘤的 CAR 细胞的试验均在黑色素瘤患者中显示出临床反应。仅在临床前模型中测试了针对黑色素瘤的 CAR 细胞，然而，针对其他组织类型（如淋巴瘤）的 CAR 细胞已在患者中引起抗肿瘤反应。
作为一种最先进的个性化医疗范例，ACT 是一种有潜力治愈转移性黑色素瘤的治疗方法。目前正在进行旨在简化方案的临床试验，可能会使更多的患者得到治疗，并使学术癌症中心能够提供 ACT。
