Abstract 3190: Enhancing chimeric antigen receptor (CAR)-T cell therapy for solid tumors through photobiomodulation

Abstract Chimeric Antigen Receptor (CAR)-T cell therapy has demonstrated remarkable success in treating hematological malignancies, yet its efficacy in solid tumors remains limited, with response rates as low as ∼9% and limited by high relapse rates (∼50% within one year). Furthermore, CAR-T therapies have demonstrated challenges for reduced efficacy, largely attributed to poor penetration and poor infiltration of CAR-T cells into the tumor microenvironment (TME), combined with immune suppressive factors such as T cell exhaustion, metabolic fatigue, and anti-inflammatory cytokines. To address these barriers, we investigate the potential of photobiomodulation (PBM), a non-invasive light-based treatment to enhance CAR-T cell function in both solid tumors and hematological malignancies. PBM, which stimulates cellular activity, could improve CAR-T cell survival, metabolic fitness, and persistence, and thus, therapeutic efficacy. Using optimized wavelengths, we evaluated CAR-T cell function in vitro, focusing on cellular metabolism and expansion. Metabolic analysis using the Seahorse XF platform revealed a marked upregulation in oxygen consumption rates (OCR) indicative of enhanced glycolytic activity (p<0.001) in CAR-T cells exposed to PBM. Furthermore, we observed a significant increase in T cell counts over a 14-day period, validated by CFSE labeling and flow cytometry with AO/PI and hemacytometer counting, in addition to evaluation of cytotoxicity and differentiation of PBM-treated CAR-T cells compared to control CAR-T cells. These findings suggest PBM preconditioning significantly enhances CAR-T cell energy production, proliferation, metabolic activity, and persistence, potentially overcoming challenges related to TME penetration, immune suppression, and exhaustion in solid tumors. Additionally, the PBM treatment could help address issues of persistence and proliferation of CAR-T cells in both solid tumors and hematological malignancies, improving their overall therapeutic potential and optimizing treatment protocols for clinical application. This combinational approach of CAR-T cell therapy and PBM represents a promising strategy to refine and optimize CAR-T functional longevity in both hematological and solid malignancies for clinical translation. As my lab experience focuses on immunology and the development of CAR-T therapies for pre-clinical use, this project will be in collaboration with the Jenkins/Moffitt Lab for their expertise in PBM. An invention disclosure was made to CWRU for the use of PBM for adoptive cell therapy. It is expected that a provisional application will be filed in the future prior to public disclosure. CWRU is the full owner of this intellectual property. Citation Format: Jude S. Franklin. Enhancing chimeric antigen receptor (CAR)-T cell therapy for solid tumors through photobiomodulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3190.