Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, 266071, China.
J Cancer Res Clin Oncol. 2023 Aug;149(10):7363-7378. doi: 10.1007/s00432-023-04683-5. Epub 2023 Mar 18.
Neoantigens produced from mutations in tumors are important targets of T-cell-based immunotherapy and immune checkpoint blockade has been approved for treating multiple solid tumors. We investigated the potential benefit of adoptive neoantigen-reactive T (NRT) cells in combination with programmed cell death protein 1 inhibitor (anti-PD1) for treating lung cancer in a mouse model.
NRT cells were prepared by co-culturing T cells and neoantigen-RNA vaccine-induced dendritic cells. Then, adoptive NRT cells in combination with anti-PD1 were administered to tumor-bearing mice. Pre- and post-therapy cytokine secretion, antitumor efficacy, and tumor microenvironment (TME) changes were determined both in vitro and in vivo.
We successfully generated NRT cells based on the 5 neoantigen epitopes identified in this study. NRT cells exhibited an enhanced cytotoxic phenotype in vitro and the combination therapy led to attenuated tumor growth. In addition, this combination strategy downregulated the expression of the inhibitory marker PD-1 on tumor-infiltrating T cells and promoted the trafficking of tumor-specific T cells to the tumor sites.
The adoptive transfer of NRT cells in association with anti-PD1 therapy can exert an antitumor effect on lung cancer, and is a feasible, effective, and novel immunotherapy regimen for treating solid tumors.
肿瘤突变产生的新抗原是 T 细胞为基础的免疫治疗的重要靶点，免疫检查点阻断已被批准用于治疗多种实体肿瘤。我们研究了过继性新抗原反应性 T（NRT）细胞与程序性死亡蛋白 1 抑制剂（抗 PD-1）联合用于治疗肺癌的潜在益处，在小鼠模型中进行了研究。
通过共培养 T 细胞和新抗原 RNA 疫苗诱导的树突状细胞来制备 NRT 细胞。然后，将过继性 NRT 细胞与抗 PD-1 联合用于荷瘤小鼠。在体外和体内测定治疗前后细胞因子分泌、抗肿瘤疗效和肿瘤微环境（TME）变化。
我们成功地基于本研究中鉴定的 5 个新抗原表位生成了 NRT 细胞。NRT 细胞在体外表现出增强的细胞毒性表型，联合治疗导致肿瘤生长减弱。此外，这种联合策略下调了肿瘤浸润 T 细胞上抑制性标记物 PD-1 的表达，并促进了肿瘤特异性 T 细胞向肿瘤部位的迁移。
与抗 PD-1 治疗相关的 NRT 细胞过继转移可对肺癌发挥抗肿瘤作用，是治疗实体肿瘤的一种可行、有效和新颖的免疫治疗方案。
