Hollander Nurit
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Crit Rev Immunol. 2009;29(5):399-418. doi: 10.1615/critrevimmunol.v29.i5.30.
Therapeutic vaccines have been developed to induce immune responses capable of eradicating lymphoma and myeloma tumors. Most of these vaccines target the immunoglobulin idiotype (Id) as a tumor-specific antigen. Phase I/II clinical trials of Id vaccination in lymphoma demonstrated that some lymphoma patients could mount immune responses that were correlated with a favorable clinical outcome. These encouraging results initiated phase III trials of Id vaccination in lymphoma, the results of which have been recently released. Disappointingly, only one of three phase III studies achieved the primary end point of progression-free survival. Detailed analysis of these results is awaited to help identify factors that determine clinical efficacy of Id vaccination as reflected in the three trials. Unlike lymphoma, studies of Id vaccination in multiple myeloma have yielded far less evidence of clinical benefit. Although Id vaccines induce immune responses in myeloma patients, their efficacy is insufficient to provide a clear clinical benefit. Strategies to improve lymphoma and myeloma vaccines are currently tested with an emphasis on optimization of antigen delivery and presentation and modulation of the immune system toward enhancement of T-cell function. Despite many hurdles yet to overcome, it is hoped that newly developed strategies that augment both immune and clinical responses will allow effective vaccination resulting in tumor eradication.
治疗性疫苗已被开发出来,以诱导能够根除淋巴瘤和骨髓瘤肿瘤的免疫反应。这些疫苗大多将免疫球蛋白独特型(Id)作为肿瘤特异性抗原。淋巴瘤Id疫苗的I/II期临床试验表明,一些淋巴瘤患者能够产生与良好临床结果相关的免疫反应。这些令人鼓舞的结果启动了淋巴瘤Id疫苗的III期试验,其结果最近已公布。令人失望的是,三项III期研究中只有一项达到了无进展生存期的主要终点。有待对这些结果进行详细分析,以帮助确定在这三项试验中反映出的决定Id疫苗临床疗效的因素。与淋巴瘤不同,多发性骨髓瘤Id疫苗的研究产生的临床获益证据要少得多。虽然Id疫苗能在骨髓瘤患者中诱导免疫反应,但其疗效不足以带来明确的临床获益。目前正在测试改善淋巴瘤和骨髓瘤疫苗的策略,重点是优化抗原递送和呈递以及调节免疫系统以增强T细胞功能。尽管仍有许多障碍有待克服,但希望新开发的增强免疫和临床反应的策略将能实现有效的疫苗接种,从而根除肿瘤。