免疫治疗已成为乳腺癌治疗的新手段。我们前期设计的B细胞疫苗（scFv-HER2）通过CD19分子单链抗体（scFv）将肿瘤抗原HER2靶向至B细胞，可增强抗肿瘤免疫应答，明显抑制乳腺癌细胞生长，但肿瘤并未根除，提示仍有部分肿瘤细胞逃逸免疫监视,而促进T细胞活化诱导细胞死亡（AICD）是肿瘤逃逸免疫监视的其中一个重要机制， 因此在前期研究基础上抑制T细胞AICD则有助于抑制肿瘤免疫逃逸。CD137分子主要表达在活化T细胞等细胞表面，其活化型抗体可降低T细胞AICD,增强T细胞杀伤效应。故项目在前期基础上偶联CD137得到新的疫苗scFv-CD137-HER2，将抗原HER2和CD137同时靶向至B细胞，期望产生抗肿瘤抗体，增强抗原特异性T细胞应答，同时通过产生的CD137抗体减少T细胞AICD，维持效应性T细胞寿命，进一步增强T细胞杀伤功能，达到长效抗肿瘤效果，为乳腺癌的临床治疗提供新思路。

Immunotherapy has become the latest clinical therapeutic intervention in breast cancer treatment. In our previous studies, we have designed the B cell vaccine (scFv-HER2) and demonstrated that targeting tumor-associated Ag HER2 to B cells via anti-CD19 single chain variable fragment (scFv) could elicit anti-tumor immune response to inhibit the growth of breast cancer cells, however, tumor was not eradicated by immune system which indicated that there are still some tumor cells evading from immune surveillance. A mechnism of tumor escape from immune surveillance is to promote activation-induced cell death (AICD) of effector T cells, so to reduce activation-induced cell death (AICD) of effector T cells will inhibit the immune escape of tumor cells. The CD137 is expressed by activated T cells, studies have shown that agonistic anti-CD137 monoclonal antibody can reduce activation-induced cell death (AICD) of effector T cells and enhance the cytotoxic activity of T cells. Based on our previous study, we plan to conjugate CD137 to get new vaccine scFv-CD137-HER2, which will target two antigens (HER2 and CD137) to B cells via CD19. Hopefully, this new strategy can elicit more effective anti-tumor antibody and enhance antigen specific T cells response, lower the activation-induced cell death of T cells, prolong the life of effector T cells and further promote the cytotoxic activity of T cells. Finally, we want to achieve the long-term anti-tumor effect and provide new ideas for the clinical treatment of breast cancer.