Intratumoral delivery of PD-1/PD-L1 and CTLA-4 inhibitors for recurrent/refractory solid tumors: a proof-of-concept treatment strategy

作者：H Tan, Neelam Shah, Bingjia He, Tianrun Liu, Tianheng Li, Manting Liu, Yingying Gu, Cheng Zhi, Yuanjun Ou, Junhao Huang, Min Li, Shaoli Zuo, Dongni Chen, Rong Qin, Hainan Yang, Xufeng Li, Hui Lian, Qingde Wu, Rom S. Leidner, Rui Chen, Ankui Yang, Lili Yang, Zhenfeng Zhang · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1669924 · 被引用次数：1 · 研究领域：Cancer Immunotherapy and Biomarkers、CAR-T cell therapy research、HER2/EGFR in Cancer Research

Background: Immune checkpoint inhibitors (ICIs) are a leading immunotherapy. However, their application has not universally translated into significant benefits. A substantial number of patients either show resistance or relapse post-initial response, which emphasizes the need for more sophisticated therapeutic approaches. The drug combination is one promising route. The cancer-immunity cycle reveals the anti-tumor immune-related rate limiting steps of tumors. Theoretically, focusing on different phases of the cancer-immunity cycle can enhance therapeutic results. However, combination therapy includes a higher risk of adverse effects, which demand careful consideration. Methods: In this study, we combined programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) and cytotoxic T Lymphocyte antigen 4 (CTLA-4) inhibitors with a reduced dosage but via an intra-tumor drug delivery strategy to treat recurrent/refractory (R/R) advanced solid tumors. Results: Herein, we report four patients with favorable outcomes (complete response for more than 2 years). In our cases, most TRAEs are of grade 1-2. Conclusion: Intratumoral co-delivery of PD-1/PD-L1 and CTLA-4 inhibitors with reduced dosage shows promising efficacy and safety in R/R advanced solid tumors. In addition to reducing drug-related adverse events, this technology has advantages in activating tumor immunity. Clinical Trial Registration: https://clinicaltrials.gov/, identifier: NCT03755739.