MYELOMA IDIOTYPE VACCINES

多发性骨髓瘤患者很少通过常规治疗治愈。 化疗骨髓高剂量治疗 移植可以治愈一些患者，但尽管显着 细胞减少仍然是移植后的高风险 复发需要额外的无毒治疗， 诱导对肿瘤Id的免疫应答， 移植后的微小残留病可能提供 这样的做法。肿瘤B细胞IG的独特型 恶性肿瘤可以被免疫系统识别为肿瘤- 特异性抗原骨髓瘤细胞、B细胞与抗原提呈 细胞可以加工并呈递MHC I类分子上的Id片段 或可被T细胞识别的II类分子。临床前 ID免疫的研究表明，这种方法可以 诱导抗Id抗体和Id特异性T细胞， 在淋巴瘤和骨髓瘤模型中的肿瘤复发或进展。 我们将测试一系列自体免疫 Id-KLH/IGM-CSF可诱导免疫后Id特异性T细胞应答 自体或同种异体BMT骨髓瘤患者。患者将 在BMT前、BMT后和整个免疫过程中进行评价 Id特异性T细胞的示意图。这些化合物的抗肿瘤活性 细胞将在那里通过克隆、扩增和评估进行测试。 体外功能在平行研究中，我们将确定并测试 最佳的抗原递送方法，有利于诱导一个 使用鼠模型的CD 8 + Id特异性CTL免疫应答 系统这些结果将用于指导下一系列的 临床试验这项建议的具体目标是： 1.评价肿瘤源性IG的免疫效果 (Id)诱导免疫反应， 自体或异体骨髓移植后骨髓瘤 移植 2.使用充分表征的小鼠淋巴瘤/骨髓瘤模型 评估新的佐剂和抗原递送系统， 并表征Id特异性T细胞。

Patients with multiple myeloma are seldom cured by conventional chemotherapy. High dose therapy with bone marrow transplantation can cure some patients, but despite significant cytoreduction there continues to be a high risk of posttransplant relapse. Additional non-toxic therapies are needed and the induction of an immune response to the tumor Id in the posttransplant setting of minimal residual disease may provide such an approach. The idiotype (Id) of the tumor Ig of B cell malignancies can be recognized by the immune system as a tumor- specific antigen. Myeloma cells, B cells and antigen presenting cells can process and present fragments of the Id on MHC class I or II molecules which can be recognized by T cells. Preclinical studies of id immunization demonstrate that this approach can induce anti-id antibodies and Id-specific T cells which prevent tumor relapse or progression in lymphoma and myeloma models. We will test whether a series Of immunizations with autologous Id-KLH/IGM-CSF can induce Id-specific T cell responses in post autologous or allogeneic BMT myeloma patients. Patients will be evaluated pre-BMT, post BMT and throughout the immunization schema for Id-specific T cells. The anti-tumor activity of these cells will be tested by cloning, expanding and evaluating there function in vitro. In parallel studies, we will determine and test optimal methods of antigen delivery that favor the induction of a CD8+ Id-specific CTL immune response using a murine model system. These results will be used to direct the next series of clinical trials. The specific aims of this proposal are: 1. to evaluate the ability of immunization with tumor derived Ig (Id) to induce immune responses in patients with multiple myeloma following autologous or allogeneic bone marrow transplant. 2. To use a well characterized murine lymphoma/myeloma model to evaluate new adjuvants and antigen deliver systems to induce and characterize Id specific T cells.