胶质母细胞瘤自噬体疫苗的制备及免疫功能研究

Immunotherapy has been becoming one of the most important supplementary means for the treatment of glioblastoma (GBM). Several of clinical and basical researches have been conducted to study the efficiency of GBM vaccines. Autophagy, which can wrap different intracellular neoplastic antigens, has been made into vaccines to inhibit the growth of malignant tumors cells such as lung cancer and melanoma. In our group’s preliminary study, GBM autophagosome vaccines was prepared using the classical autophagosome-activating drug, rapamycin, and was proved to possess immunogenicity and the capacity of promoting the proliferation of lymphocytes in vitro. In order to further optimize this vaccine, we found the third generation platinum drugs, oxaliplatin, was able to induce the genesis of autophagy and enhance the anti-tumor immunological response. In this study, we plan to make another autophagy vaccine using oxaliplatin, and compare the immunological differences between oxaliplatin-induced and rapamycin-induced GBM autophagy vaccines, including the immunological competence and antineoplastic capacity in vitro and in vivo. In this way we can optimize the production of GBM autophagy vaccines, improve the immunogenicity of tumor vaccines, and pave the way for clinical research by providing experimental basis and theoretical endorsement.

免疫治疗已经成为胶质母细胞瘤（GBM）临床治疗的重要辅助手段。已有多种方法制备的胶质母细胞瘤疫苗进行了临床和基础研究。自噬体可选择性包裹多种细胞内肿瘤抗原物质，已被制成疫苗，抑制肺癌、黑色素瘤等恶性肿瘤细胞的生长。本课题组的前期研究中，已成功用经典促自噬体药物——雷帕霉素，制备出GBM自噬体疫苗，证实其具有体外免疫原性和促进淋巴细胞增殖的作用。为进一步优化疫苗，我们发现三代铂类药物——奥沙利铂，具有诱导自噬体发生，增强抗肿瘤免疫应答的作用。本研究计划用奥沙利铂制备出第二种GBM自噬体疫苗，比较奥沙利铂GBM自噬体疫苗和雷帕霉素GBM自噬体疫苗的免疫功能的区别，包括体内和体外免疫活性和抑制肿瘤生长的作用等。从而优化GBM自噬体疫苗的制备方法，提高肿瘤疫苗的免疫原性，为其进入临床研究提供实验依据和理论支持。

胶质母细胞瘤（GBM）是当今神经恶性肿瘤的巨大挑战。目前，免疫治疗已经成为胶质母细胞瘤标准化治疗外的重要辅助手段。已有多种胶质母细胞瘤疫苗进行了临床和基础研究。课题组拟在前期基础上，提出科学假设“胶质母细胞瘤自噬体疫苗的制备及免疫功能研究”。用不同诱导方案所得的自噬体抗原致敏DCs。用体外及小鼠颅内模型研究胶质母细胞瘤自噬体疫苗对胶质母细胞瘤的抗肿瘤免疫应答。在课题实施中，用多种自噬药物诱导方案，优化自噬体的提取、纯化方案，显著提升了所得胶质母细胞瘤自噬体的产量及纯度。并揭示了该自噬体抗原的潜在免疫活性。本课题的实施将揭示自噬体疫苗对胶质母细胞瘤小鼠颅内模型的作用，为其进入临床研究提供实验依据和理论支持。