Chu Jiacheng, Wang Chenya, Ma Qingle, Dai Huaxing, Xu Jialu, Ogunnaike Edikan A, Peng Fei, Shi Xiaolin, Wang Chao
Institute of Functional Nano & Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, China.
Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Cytotherapy. 2022 Mar;24(3):291-301. doi: 10.1016/j.jcyt.2021.08.004. Epub 2021 Oct 21.
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has shown great success in clinical trials. Programmed cell death 1 (PD-1)-expressing TILs show high specificity to autologous tumor cells. However, limited therapeutic efficiency is observed as a result of the tumor immune microenvironment (TIME).
Coupling PD-1ex vivo-derived TILs with a monoclonal antibody against anti-PD-1 (aPD-1) reinvigorated the anti-tumor response of TILs against solid tumor without altering their high tumor targeting ability.
Using a melanoma-bearing mouse model, PD-1 TILs blocked with aPD-1 (PD-1 TILs-aPD-1) exhibited a high capability for tumor targeting as well as improved anti-tumor response in TIME. Tumor growth was substantially delayed in the mice treated with PD-1 TILs-aPD-1.
The strategy utilizing TIL therapy coupled with immune checkpoint antibodies may extend to other therapeutic targets of ACT.
采用肿瘤浸润淋巴细胞（TILs）进行过继性细胞治疗（ACT）在临床试验中已取得巨大成功。表达程序性细胞死亡蛋白1（PD-1）的TILs对自体肿瘤细胞表现出高度特异性。然而，由于肿瘤免疫微环境（TIME），观察到治疗效率有限。
将体外获得的PD-1 TILs与抗PD-1单克隆抗体（aPD-1）偶联，可恢复TILs对实体瘤的抗肿瘤反应，而不会改变其高肿瘤靶向能力。
使用荷黑素瘤小鼠模型，用aPD-1阻断的PD-1 TILs（PD-1 TILs-aPD-1）在TIME中表现出高肿瘤靶向能力以及改善的抗肿瘤反应。用PD-1 TILs-aPD-1治疗的小鼠肿瘤生长明显延迟。
利用TIL治疗与免疫检查点抗体相结合的策略可能扩展到ACT的其他治疗靶点。
