Yale Cancer Center, 333 Cedar Street, FMP #126, New Haven, CT 06525, USA.
Curr Oncol Rep. 2009 Sep;11(5):397-404. doi: 10.1007/s11912-009-0053-z.
Immunotherapy is an effective treatment option for a small percentage of patients with advanced melanoma or at high risk for recurrence after resection of the primary tumor. However, a long period of unsuccessful immune modulation trials involving new cytokines, antibodies, cancer vaccines, adoptive immunotherapy, and combinations generated doubts that benefit could be extended to a larger group of patients. Renewed optimism for the therapeutic potential of immune therapy is currently driven by key advances in tumor immunobiology, including the potential to manipulate and disrupt immune activation checkpoints and tumor defense mechanisms; newer approaches to antigen presentation for immune activation; refinements to procedures for antigen-specific T-cell expansions in vitro and preparative regimens to support their expansion and activity in vivo; gene transfer to alter lymphocyte specificity and function; and the potential for discovery of improved predictive biomarkers to select patients for individual treatments. Proof of concept is provided by durable remissions observed in patients with advanced melanoma enrolled in clinical trials of anti-CTLA-4 and in new studies of adoptively transferred tumor antigen-specific lymphocytes combined with lymphocyte ablation conditioning regimens. Many agents now being developed are predicted to produce broader, more potent, and more effective antitumor immune responses.
免疫疗法是治疗小部分晚期黑色素瘤患者或原发性肿瘤切除后复发风险高的患者的有效治疗选择。然而，新细胞因子、抗体、癌症疫苗、过继免疫疗法和组合的免疫调节试验长期未取得成功，这让人怀疑是否可以将获益扩展到更大的患者群体。目前，对免疫疗法治疗潜力的重新乐观情绪，主要来自肿瘤免疫生物学的关键进展，包括操纵和破坏免疫激活检查点和肿瘤防御机制的潜力；用于免疫激活的新型抗原呈递方法；体外抗原特异性 T 细胞扩增程序的改进和支持其在体内扩增和活性的预备方案；改变淋巴细胞特异性和功能的基因转移；以及发现改善的预测生物标志物来选择患者进行个体化治疗的潜力。在接受抗 CTLA-4 临床试验和新的过继转移肿瘤抗原特异性淋巴细胞联合淋巴细胞消融调理方案研究的晚期黑色素瘤患者中观察到持久缓解，为这一概念提供了证据。目前正在开发的许多药物预计将产生更广泛、更有效和更有效的抗肿瘤免疫反应。
