Division of Oncology, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
Curr Pharm Des. 2010 Jan;16(3):300-7. doi: 10.2174/138161210790170111.
After twenty years of use in humans, customized idiotypic vaccination yet remains a non-approved, experimental therapeutic option for patients with lymphoma and myeloma. Potentially applicable to all B-cell malignancies whose cells express a clonal immunoglobulin or its epitopes on their surface, this treatment is designed to prevent disease recurrence or progression. Mostly used in follicular lymphoma patients so far, idiotype vaccines have clearly shown biological efficacy, clinical efficacy and clinical benefit in this setting, although no study aiming at regulatory approval of the procedure has been able to meet its main clinical endpoints. In mantle cell lymphoma, only biological efficacy has been proven for idiotypic vaccination, while in multiple myeloma a limited number of studies support the notion of biological and perhaps even clinical efficacy, although no credible evidence of clinical benefit has still emerged. Idiotype vaccines have been produced and administered in a number of substantially different manners. Therefore, the results of most clinical trials cannot be easily compared, and even less pooled together in meaningful meta-analyses. A more creative and yet scientifically sound way to design clinical trials of customized active immunotherapies will be key to the future development of idiotype vaccines, particularly considering that we currently lack any clinical or biological indicator to possibly predict which patients are more likely to respond to idiotypic vaccination from an immunologic point of view. This review aims at summarizing the multifaceted success achieved by idiotype vaccines, as well as at outlining the challenges awaiting them in the near future: how to improve feasibility, immunogenicity and efficacy, as well as how to confirm benefit and gain regulatory approval.
在人类中使用二十年后，定制的独特型疫苗仍然是非批准的、实验性的淋巴瘤和骨髓瘤患者治疗选择。这种治疗方法可能适用于所有在其表面表达克隆免疫球蛋白或其表位的 B 细胞恶性肿瘤，旨在预防疾病复发或进展。迄今为止，这种治疗方法主要用于滤泡性淋巴瘤患者，在这种情况下，独特型疫苗已明显显示出生物学疗效、临床疗效和临床获益，尽管尚无旨在监管批准该程序的研究能够达到其主要临床终点。在套细胞淋巴瘤中，独特型疫苗仅证明了生物学疗效，而在多发性骨髓瘤中，只有少数研究支持独特型疫苗具有生物学甚至可能是临床疗效的观点，尽管仍未出现可靠的临床获益证据。独特型疫苗已经以多种截然不同的方式生产和给药。因此，大多数临床试验的结果不容易比较，更不用说在有意义的荟萃分析中组合在一起了。设计定制主动免疫疗法临床试验的更具创新性且科学合理的方法将是未来独特型疫苗发展的关键，特别是考虑到我们目前缺乏任何临床或生物学指标来可能预测从免疫学角度来看，哪些患者更有可能对独特型疫苗产生反应。这篇综述旨在总结独特型疫苗取得的多方面成功，并概述它们在不久的将来面临的挑战：如何提高可行性、免疫原性和疗效，以及如何确认获益和获得监管批准。
