Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Washington University School of Medicine, St. Louis, MO, USA.
Cancer Cell. 2022 Sep 12;40(9):1010-1026.e11. doi: 10.1016/j.ccell.2022.08.003. Epub 2022 Aug 25.
Neoantigens arising from mutations in tumor DNA provide targets for immune-based therapy. Here, we report the clinical and immune data from a Phase Ib clinical trial of a personalized neoantigen-vaccine NEO-PV-01 in combination with pemetrexed, carboplatin, and pembrolizumab as first-line therapy for advanced non-squamous non-small cell lung cancer (NSCLC). This analysis of 38 patients treated with the regimen demonstrated no treatment-related serious adverse events. Multiple parameters including baseline tumor immune infiltration and on-treatment circulating tumor DNA levels were highly correlated with clinical response. De novo neoantigen-specific CD4 and CD8 T cell responses were observed post-vaccination. Epitope spread to non-vaccinating neoantigens, including responses to KRAS G12C and G12V mutations, were detected post-vaccination. Neoantigen-specific CD4 T cells generated post-vaccination revealed effector and cytotoxic phenotypes with increased CD4 T cell infiltration in the post-vaccine tumor biopsy. Collectively, these data support the safety and immunogenicity of this regimen in advanced non-squamous NSCLC.
肿瘤 DNA 突变产生的新抗原为免疫治疗提供了靶点。在这里，我们报告了一项 I 期临床试验的临床和免疫数据，该试验将个体化新抗原疫苗 NEO-PV-01 与培美曲塞、卡铂和帕博利珠单抗联合用于晚期非鳞状非小细胞肺癌 (NSCLC) 的一线治疗。对 38 例接受该方案治疗的患者的分析表明，没有与治疗相关的严重不良事件。包括基线肿瘤免疫浸润和治疗期间循环肿瘤 DNA 水平在内的多个参数与临床反应高度相关。接种疫苗后可观察到新抗原特异性 CD4 和 CD8 T 细胞反应。接种疫苗后还检测到抗原表位扩展到非疫苗新抗原，包括对 KRAS G12C 和 G12V 突变的反应。接种疫苗后产生的新抗原特异性 CD4 T 细胞表现出效应和细胞毒性表型，在接种疫苗后的肿瘤活检中 CD4 T 细胞浸润增加。总的来说，这些数据支持该方案在晚期非鳞状 NSCLC 中的安全性和免疫原性。
