MONOCLONAL ANTIBODY ANTI-IDIOTYPE TUMOR VACCINES

本项目的主要目标是开发单克隆抗体， 抗体（MoAb）抗独特型（抗Id）肿瘤疫苗 治疗人类癌症。 第二阶段的具体目标 建议是开发抗Id单克隆抗体疫苗， 神经内分泌肿瘤相关抗原（TAA）的内部图像 人黑色素瘤、神经母细胞瘤和小细胞肺 癌（SCLC）和实验大鼠神经内分泌动物 肿瘤模型 我们还打算生产合成肽疫苗 对应于整个单克隆抗体的内部抗原独特位 疫苗制剂。 肽亚单位的施用 独特位疫苗可以最大限度地减少潜在的并发症 用全鼠重复免疫人类受试者 MoAbs 单克隆抗体和多肽抗Id疫苗的制备 将在动物肿瘤模型中测试抗肿瘤作用， 在人类实验对象中。 这些体内研究的结果应 确定那些最适合进一步研究的抗Id疫苗制剂 在人类受试者中进行的临床试验。 在 与常规纯化的TAA疫苗相比，抗Id单克隆抗体 制剂可以容易地大量生产 用于增强对弱免疫原性TAA的免疫应答 决定簇，包括碳水化合物和脂质部分。 再- II期研究的结果，结合固有优势 抗Id疫苗制剂，可能会导致发展 用于治疗人类肿瘤的新的肿瘤疫苗产品 癌的

The main objective of this project is to develop monoclonal antibody (MoAb) anti- idiotype (anti-Id) tumor vaccines for the treatment of human cancer. The specific aims of this Phase 2 proposal are to develop anti-Id MoAb vaccines that represent internal images of neuroendocrine tumor-associated antigens (TAA) expressed by human melanoma, neuroblastoma and small cell lung carcinomas (SCLC) and by an experimental rat neuroendocrine animal tumor model. We also intend to generate synthetic peptide vaccines corresponding to the internal antigen idiotopes of whole MoAb vaccine preparations. The administration of peptide subunit idiotope vaccines may minimize potential complications associated with repeated immunization of human subjects with whole murine MoAbs. The whole MoAb and peptide anti-Id vaccine preparations will be tested for anti-tumor effects in the animal tumor model and in human subjects. The results of these in vivo studies should identify those anti-Id vaccine preparations best suited for further clinical trials in human subjects during the Phase 3 effort. In contrast to conventionally purified TAA vaccines, MoAb anti-Id preparations can be readily produced in large quantities and may be employed to enhance immune responses to weakly immunogenic TAA determinants, including carbohydrate and lipid moieties. The re- sults of the Phase 2 studies, combined with the inherent advantages of anti-Id vaccine preparations, may lead to the development of novel tumor vaccine products useful in the therapy of human cancers.