MYELOMA IDIOTYPE VACCINES

多发性骨髓瘤患者很少用传统的方法治愈 化疗。大剂量骨髓治疗 移植可以治愈一些患者，但尽管意义重大 细胞减少移植后的风险仍然很高 旧病复发。需要更多的无毒疗法，而 在小鼠体内诱导对肿瘤ID的免疫反应 移植后微小残留病的设置可能会提供 这样一种方法。B细胞肿瘤免疫球蛋白的独特型 恶性肿瘤可以被免疫系统识别为肿瘤- 特定的抗原。骨髓瘤细胞、B细胞与抗原提呈 细胞可以处理和呈现MHC I类上的ID片段 或者是T细胞可以识别的II类分子。临床前 对身份免疫的研究表明，这种方法可以 诱导抗id抗体和ID特异性T细胞，防止 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是否 ID-KLH/IGM-CSF可诱导ID特异性T细胞反应 自体或异基因骨髓瘤患者。病人将会是 在骨髓移植前、骨髓移植后和整个免疫过程中进行评估 ID特定的T细胞的模式。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 在体外发挥作用。在平行研究中，我们将确定和测试 最佳的抗原递送方法，有利于诱导 利用小鼠模型进行CD8+ID特异性CTL免疫应答 系统。这些结果将被用来指导下一系列 临床试验。这项建议的具体目标是： 1.评价肿瘤来源免疫球蛋白的免疫效果。 (ID)诱导多发性硬化症患者的免疫反应 自体或异基因骨髓后的骨髓瘤 移植。 2.使用具有良好特性的小鼠淋巴瘤/骨髓瘤模型 评估新的佐剂和抗原递送系统以诱导 并鉴定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.