College of Life Science and Technology, Jinan University, Guangzhou, People's Republic of China.
Jinan University Affiliated Guangdong 999 Brain Hospital, Guangzhou, People's Republic of China.
Cancer Immunol Immunother. 2020 Jul;69(7):1375-1387. doi: 10.1007/s00262-020-02496-w. Epub 2020 Feb 20.
Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3-13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4 and/or CD8 T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4 and CD8 T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.Trial registration ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).
肿瘤相关抗原（TAA）已在癌症治疗的各种临床试验中进行了测试，但针对个体 TAA 免疫的特异性 T 细胞反应模式仍有待充分了解。我们报告了用个性化 TAA 面板脉冲处理树突状细胞疫苗免疫的患者中的抗原特异性 T 细胞反应。首先分析患者的肿瘤样本以鉴定过表达的 TAA。然后用预先制造的编码全长 TAA 的 mRNA 转染自体 DC，这些 TAA 在患者的肿瘤中过表达。多形性胶质母细胞瘤（GBM）或晚期肺癌患者接受了用个性化 TAA 面板转染的 DC 疫苗，联合低剂量环磷酰胺、聚 I：C、咪喹莫特和抗 PD-1 抗体。测量了抗原特异性 T 细胞反应。评估了安全性和疗效。总共 10 名患者接受了用个性化 TAA 面板转染的 DC 疫苗治疗，该面板包含 3-13 种不同的 TAA。在对 7 名抗 TAA T 细胞反应进行测试的患者中，大多数 TAA 诱导了抗原特异性 CD4 和/或 CD8 T 细胞反应，而不管它们在肿瘤组织中的表达水平如何。这些患者中未观察到 3/4 级不良事件。此外，与同一机构接受标准治疗的患者相比，接受治疗的患者的总生存期较好。个性化 TAA 免疫诱导特异性 CD4 和 CD8 T 细胞反应，无明显自身免疫性不良事件，并与良好的总生存期相关。这些结果支持对个体化 TAA 面板的 DC 免疫进行进一步研究，以用于实体瘤患者的联合免疫治疗方案。
ClinicalTrials.gov，NCT02709616（2016 年 3 月），NCT02808364（2016 年 6 月），NCT02808416（2016 年 6 月）。
