Intratumoral delivery of PD-1/PD-L1 and CTLA-4 inhibitors for recurrent/refractory solid tumors: a proof-of-concept treatment strategy.
Publication Title
Front Immunol
Document Type
Article
Publication Date
1-1-2025
Keywords
Adult; Aged; Female; Humans; Male; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; CTLA-4 Antigen; Drug Resistance, Neoplasm; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasm Recurrence, Local; Neoplasms; Programmed Cell Death 1 Receptor; Proof of Concept Study; Treatment Outcome; CTLA-4 inhibitor; PD-1/PD-L1 inhibitors; clinical trial; intratumoral injection; recurrent/refractory advanced solid tumor.; oregon; chiles
Abstract
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.
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
DOI
10.3389/fimmu.2025.1669924
