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.

多发性骨髓瘤的患者很少被常规治疗 化学疗法。骨髓高剂量治疗 移植可以治愈某些患者，但尽管很明显 细胞减少术仍然存在移植后的高风险 复发。需要其他无毒疗法，并且 诱导对肿瘤ID的免疫反应 移植后的残留疾病的设置可能会提供 这样的方法。 B细胞的肿瘤Ig的白痴（ID） 免疫系统可以将恶性肿瘤识别为肿瘤 特异性抗原。骨髓瘤细胞，B细胞和抗原呈现 单元可以在MHC I类上处理并呈现ID的片段 或可以由T细胞识别的II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，以防止 淋巴瘤和骨髓瘤模型的肿瘤复发或进展。 我们将测试一系列自体免疫 ID-KLH/IGM-CSF可以在POST中诱导ID特定的T细胞响应 自体或同种异体BMT骨髓瘤患者。患者会 评估了BMT前BMT和整个免疫 ID特异性T细胞的模式。这些的抗肿瘤活性 细胞将通过克隆，扩展和评估在那里测试 体外功能。在平行研究中，我们将确定和测试 有利于诱导的抗原递送的最佳方法 CD8+ ID特异性CTL免疫反应使用鼠模型 系统。这些结果将用于指导下一个系列 临床试验。该提案的具体目的是： 1。评估肿瘤衍生的Ig免疫的能力 （ID）诱导多个患者的免疫反应 自体或同种异体骨髓后的骨髓瘤 移植。 2。使用良好的鼠淋巴瘤/骨髓瘤模型 评估新的佐剂和抗原传递系统以诱导 并表征特定的T细胞。