MYELOMA IDIOTYPE VACCINES

骨髓瘤独特型疫苗

• 批准号: 2642947
• 负责人: DAVID G MALONEY
• 金额: $ 10万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2642947
• 关键词: autologous transplantation; bone marrow transplantation; clinical research; homologous transplantation; human subject; human therapy evaluation; immunoglobulin idiotypes; laboratory mouse; multiple myeloma; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine

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.

多发性骨髓瘤患者通过常规治疗很少能治愈 化疗。高剂量骨髓治疗 移植可以治愈一些患者，但尽管显着 细胞减灭术仍然存在移植后的高风险 复发。需要额外的无毒疗法 诱导对肿瘤 Id 的免疫应答 移植后微小残留病的设置可能会提供 这样的做法。 B细胞肿瘤Ig的独特型(Id) 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 细胞和抗原呈递 细胞可以处理并呈递 I 类 MHC 上的 Id 片段 或可以被T细胞识别的II分子。临床前 体内免疫研究表明，这种方法可以 诱导抗 id 抗体和 Id 特异性 T 细胞，从而预防 淋巴瘤和骨髓瘤模型中的肿瘤复发或进展。 我们将测试是否进行一系列自体免疫接种 Id-KLH/IGM-CSF 可以诱导 Id 特异性 T 细胞反应 自体或同种异体 BMT 骨髓瘤患者。患者将会 评估 BMT 前、BMT 后和整个免疫接种过程 Id 特异性 T 细胞的模式。这些物质的抗肿瘤活性 细胞将在那里通过克隆、扩增和评估进行测试 体外发挥作用。在平行研究中，我们将确定并测试 有利于诱导的抗原递送的最佳方法 使用小鼠模型的 CD8+ Id 特异性 CTL 免疫反应 系统。这些结果将用于指导下一系列 临床试验。该提案的具体目标是： 1.评价肿瘤源性Ig的免疫能力 (Id) 诱导患有多种疾病的患者的免疫反应 自体或同种异体骨髓后发生的骨髓瘤 移植。 2. 使用特征明确的小鼠淋巴瘤/骨髓瘤模型 评估新佐剂和抗原递送系统以诱导 并表征Id特异性T细胞。