Abstract
Abstract Despite the rapid development of anti-cancer immunotherapy, the prognosis of hepatocellular carcinoma (HCC) patients is far from satisfactory. Glypican-3 (GPC3) CAR-T cell therapy has shown varied patient response. One of the potential reasons of low response rates may be due to the limited CAR-T cell infiltration. Therefore, locoregional GPC3 CAR-T therapy has been a promising option, with a hope of enhancing CAR-T cell tumor penetration. In this study, the therapeutic efficacy and underlying mechanisms of locoregional GPC3 CAR-T cell delivery were explored using HCC mouse xenografts. Orthotopic NOD-scid IL2Rgnull (NSG) HCC models were established by tumor fragment implantation into the liver. CAR-T cell injections were performed via the tail vein and portal vein to simulate systemic and locoregional administrations, respectively. Compared to the systemic treatment, locoregional therapy could better control the tumor growth, and was associated with improved liver function. In addition, the locoregional therapy group demonstrated a higher percentage of tumor-infiltrating CAR-T cells which showed an increased expression level of the cytotoxicity marker GZMB and a reduced level of the exhaustion marker LAG3. Moreover, significantly higher IFN-gamma level was found in the blood of the locoregional therapy group, indicating a better CAR-T cell functionality. In conclusion, we have demonstrated that locoregional administration of CAR-T cells is associated with increased CAR-T cell infiltration and better therapeutic efficacy. Additionally, CAR-T cells being injected locoregionally are correlated with enhanced functionality and reduced exhaustion phenotype. These findings highlight the potential of locoregional GPC3 CAR-T therapy as a promising treatment strategy for HCC patients. Citation Format: Jue Wang, Kinching Tsang, Jiale Qiu, Bo Feng. Locoregional GPC3 chimeric antigen receptor (CAR)-T cell therapy is associated with improved tumor control in hepatocellular carcinoma by enhancing CAR-T cell trafficking and functionality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4011.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
