Hurvitz Sara A, Timmerman John M
Division of Hematology/Oncology, Center for Health Sciences, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Curr Opin Oncol. 2005 Sep;17(5):432-40. doi: 10.1097/01.cco.0000174040.52427.83.
Therapeutic vaccines targeting B cell lymphoma idiotype have reached an advanced stage of clinical development, with three multicenter randomized clinical trials ongoing. This review describes the rationale and development of this immunotherapeutic approach, the design of current phase III trials, and other active vaccination approaches likely to move forward into clinical testing for lymphomas.
Several groups have achieved promising results in phase II trials of patient-specific idiotype vaccines, with very few side effects noted. Anti-idiotype antibodies, in addition to cytotoxic T cells, are now believed to be important effectors of antitumor immunity after idiotype vaccination. The manufacturing of autologous tumor idiotype proteins is being rapidly refined by the use of molecular technologies. Two trials involving more than 1000 patients are now under way, which use idiotype vaccination after induction chemotherapy; one trial completed accrual in early 2004. A third trial opened in 2004, using rituximab followed by idiotype vaccine with maintenance booster vaccines continuing throughout the period of normal B cell recovery. In accordance with the United States Food and Drug Administration, progression-free survival serves as the accepted primary efficacy endpoint in these studies.
Lymphoma idiotype vaccination represents a promising immunotherapeutic approach targeting a patient-specific tumor antigen. The results of pivotal phase III trials for three first-generation idiotype vaccines will become available in the next several years. Advanced manufacturing techniques should permit application of this tailor-made treatment to large numbers of non-Hodgkin's lymphoma patients.
针对B细胞淋巴瘤独特型的治疗性疫苗已进入临床开发的高级阶段，目前有三项多中心随机临床试验正在进行。本综述描述了这种免疫治疗方法的基本原理和发展情况、当前III期试验的设计，以及其他可能推进至淋巴瘤临床测试的主动免疫方法。
多个研究团队在患者特异性独特型疫苗的II期试验中取得了有前景的结果，且副作用极少。除细胞毒性T细胞外，抗独特型抗体现在被认为是独特型疫苗接种后抗肿瘤免疫的重要效应因子。利用分子技术，自体肿瘤独特型蛋白的生产正在迅速完善。目前正在进行两项涉及1000多名患者的试验，即在诱导化疗后使用独特型疫苗接种；一项试验于2004年初完成入组。第三项试验于2004年启动，使用利妥昔单抗，随后接种独特型疫苗，并在整个正常B细胞恢复期间持续进行维持加强疫苗接种。根据美国食品药品监督管理局的规定，无进展生存期是这些研究中公认的主要疗效终点。
淋巴瘤独特型疫苗接种是一种针对患者特异性肿瘤抗原的有前景的免疫治疗方法。三种第一代独特型疫苗的关键III期试验结果将在未来几年公布。先进的生产技术应能使这种量身定制的治疗方法应用于大量非霍奇金淋巴瘤患者。
