Rotte Anand, Bhandaru Madhuri, Zhou Youwen, McElwee Kevin J
Department of Dermatology and Skin Science, University of British Columbia, Research Pavilion, 828 West, 10th Avenue, Vancouver, BC, V5Z 1L8, Canada,
Cancer Metastasis Rev. 2015 Mar;34(1):115-28. doi: 10.1007/s10555-014-9542-0.
Metastatic melanoma is notorious for its immune evasion and resistance to conventional chemotherapy. The recent success of ipilimumab, a human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), in increasing the median survival time and stabilizing the disease progression renewed, hopes in treatment for melanoma. Currently, ipilimumab and high-dose interleukin-2 (IL-2; Aldesleukin) are approved as monotherapies for the treatment of patients with unresectable advanced melanoma, and pegylated interferon-α2b (p-IFN-α2b) is approved as an adjuvant for the treatment of patients with surgically resected high-risk melanoma. The present review describes the currently approved immune-modulators and the promising immune-based interventions that are currently in clinical trials. We present the four commonly used strategies to boost immune responses against the tumors; monoclonal antibodies, cytokines, cancer vaccines, and adoptive T cell transfer. The corresponding lists of ongoing clinical trials include details of the trial phase, target patients, intervention details, status of the study, and expected date of completion. Further, our review discusses the challenges faced by immunotherapy and the various strategies adopted to overcome them.
转移性黑色素瘤因其免疫逃逸和对传统化疗的耐药性而声名狼藉。抗细胞毒性T淋巴细胞相关抗原4(CTLA-4)的人源单克隆抗体伊匹单抗在延长中位生存时间和稳定疾病进展方面取得的近期成功,重新燃起了黑色素瘤治疗的希望。目前,伊匹单抗和高剂量白细胞介素-2(IL-2;阿地白介素)被批准作为不可切除的晚期黑色素瘤患者的单一疗法,聚乙二醇化干扰素-α2b(p-IFN-α2b)被批准作为手术切除的高危黑色素瘤患者的辅助治疗药物。本综述描述了目前已获批准的免疫调节剂以及目前正在进行临床试验的有前景的基于免疫的干预措施。我们介绍了四种常用的增强针对肿瘤的免疫反应的策略:单克隆抗体、细胞因子、癌症疫苗和过继性T细胞转移。正在进行的临床试验的相应列表包括试验阶段、目标患者、干预细节、研究状态和预期完成日期的详细信息。此外,我们的综述讨论了免疫疗法面临的挑战以及为克服这些挑战而采取的各种策略。