Shi Sanyuan, Zhang Luchen, Zheng Anjie, Xie Fang, Kesse Samuel, Yang Yang, Peng Jinliang, Xu Yuhong
School of Pharmacy, Shanghai Jiao Tong University, No.800, Dongchuan Rd, Shanghai, 200240, People's Republic of China.
School of Pharmacy, Dali University, No. 22, Snowman Rd, Dali City, 671000, People's Republic of China.
Cancer Immunol Immunother. 2024 Oct 3;73(12):248. doi: 10.1007/s00262-024-03838-8.
Tumor-reactive T cells play a crucial role in anti-tumor responses, but T cells induced by DNA vaccination are time-consuming processes and exhibit limited anti-tumor efficacy. Therefore, we evaluated the anti-tumor effectiveness of reactive T cells elicited by electroporation (EP)-mediated DNA vaccine targeting epidermal growth factor receptor variant III (pEGFRvIII plasmid), in conjunction with adoptive cell therapy (ACT), involving the transfer of lymphocytes from a pEGFRvIII EP-vaccinated healthy donor.
The validation of the established pEGFRvIII plasmid and EGFRvIII-positive cell model was confirmed through immunofluorescence and western blot analysis. Flow cytometry and cytotoxicity assays were performed to evaluate the functionality of antigen-specific reactive T cells induced by EP-mediated pEGFRvIII vaccines, ACT, or their combination. The anti-tumor effectiveness of EP-mediated pEGFRvIII vaccines alone or combined with ACT was evaluated in the B16F10-EGFRvIII tumor model.
EP-mediated pEGFRvIII vaccines elicited serum antibodies and a robust cellular immune response in both healthy and tumor-bearing mice. However, this response only marginally inhibited early-stage tumor growth in established tumor models. EP-mediated pEGFRvIII vaccination followed by adoptive transfer of lymphocytes from vaccinated healthy donors led to notable anti-tumor efficacy, attributed to the synergistic action of antigen-specific CD4 Th1 cells supplemented by ACT and antigen-specific CD8 T cells elicited by the EP-mediated DNA vaccination.
Our preclinical studies results demonstrate an enhanced anti-tumor efficacy of EP-mediated DNA vaccination boosted with adoptively transferred, vaccinated healthy donor-derived allogeneic lymphocytes.
肿瘤反应性T细胞在抗肿瘤反应中起关键作用，但DNA疫苗诱导的T细胞过程耗时且抗肿瘤疗效有限。因此，我们评估了电穿孔（EP）介导的靶向表皮生长因子受体变体III（pEGFRvIII质粒）的DNA疫苗引发的反应性T细胞的抗肿瘤效果，并结合过继性细胞疗法（ACT），该疗法涉及从接种pEGFRvIII EP疫苗的健康供体转移淋巴细胞。
通过免疫荧光和蛋白质印迹分析确认已建立的pEGFRvIII质粒和EGFRvIII阳性细胞模型的有效性。进行流式细胞术和细胞毒性测定，以评估EP介导的pEGFRvIII疫苗、ACT或它们的组合诱导的抗原特异性反应性T细胞的功能。在B16F10-EGFRvIII肿瘤模型中评估单独使用EP介导的pEGFRvIII疫苗或与ACT联合使用的抗肿瘤效果。
结果：EP介导的pEGFRvIII疫苗在健康小鼠和荷瘤小鼠中均引发了血清抗体和强大的细胞免疫反应。然而，在已建立的肿瘤模型中，这种反应仅对早期肿瘤生长有轻微抑制作用。EP介导的pEGFRvIII疫苗接种后，过继转移来自接种疫苗的健康供体的淋巴细胞，产生了显著的抗肿瘤效果，这归因于ACT补充的抗原特异性CD4 Th1细胞和EP介导的DNA疫苗引发的抗原特异性CD8 T细胞的协同作用。
我们的临床前研究结果表明，通过过继转移接种疫苗的健康供体来源的同种异体淋巴细胞增强了EP介导的DNA疫苗的抗肿瘤疗效。
