Veelken Hendrik, Osterroth Frank
Department of Internal Medicine I, Freiburg University Medical Center, Germany.
Oncology. 2002;62(3):187-200. doi: 10.1159/000059565.
Malignant lymphomas are clonal neoplasms of lymphoid origin. By definition, all cells of the malignant clone have undergone the same rearrangement of antigen receptor genes and express identical antigen receptor molecules (immunoglobulin for B cell lymphomas, T cell receptor for T cell lymphomas). The hypervariable stretches within the variable regions of these receptors are considered true tumor-specific antigens ('idiotypes'). In several animal models, protective humoral or cellular immunity can be induced against the malignant lymphoma by vaccination with the tumor-derived idiotype. Successful experimental immunization strategies in animals include idiotype protein vaccines combined with various adjuvants, genetically or immunologically modified lymphoma cells, idiotype-presenting dendritic cells, idiotype-encoding viral vectors, and DNA immunization. Firm evidence for the induction of lymphoma-specific immunity has also been obtained from human idiotype vaccination trials. Furthermore, some trials have provided strong but hitherto formally unproven evidence for clinical benefit of idiotype-vaccinated patients. Alternative vaccination approaches are based on immunologically modified tumor cells. Current research efforts concentrate on the identification of the most efficacious vaccination route, on definitive proof of clinical efficacy, and on the development of convenient methods to manufacture individual idiotype vaccines.
恶性淋巴瘤是淋巴起源的克隆性肿瘤。根据定义，恶性克隆的所有细胞都经历了相同的抗原受体基因重排，并表达相同的抗原受体分子（B细胞淋巴瘤为免疫球蛋白，T细胞淋巴瘤为T细胞受体）。这些受体可变区内的高变区被认为是真正的肿瘤特异性抗原（“独特型”）。在几种动物模型中，通过用肿瘤衍生的独特型进行疫苗接种，可以诱导针对恶性淋巴瘤的保护性体液免疫或细胞免疫。动物实验性免疫策略包括与各种佐剂联合使用的独特型蛋白疫苗、基因或免疫修饰的淋巴瘤细胞、呈递独特型的树突状细胞、编码独特型的病毒载体以及DNA免疫。在人类独特型疫苗接种试验中也获得了诱导淋巴瘤特异性免疫的确凿证据。此外，一些试验为接种独特型疫苗的患者带来临床益处提供了有力但迄今尚未得到正式证实的证据。替代疫苗接种方法基于免疫修饰的肿瘤细胞。目前的研究工作集中在确定最有效的接种途径、临床疗效的确切证据以及开发生产个性化独特型疫苗的便捷方法。
