Abstract B035: Enhanced tumor infiltration and functionality of anti-GPC3 CAR-T cells in hepatocellular carcinoma through locoregional administration

Abstract Despite the rapid development of anti-cancer immunotherapy, the prognosis of hepatocellular carcinoma (HCC) patients is far from satisfactory. GPC3 CAR-T cell therapy has shown varied patient response. One of the potential reasons of low response rates is due to the limited CAR-T cell infiltration. Therefore, locoregional GPC3 CAR-T therapy has been a promising option, with a hope of increasing the treatment efficacy. In this study, the therapeutic efficacy and underlying mechanisms of locoregional GPC3 CAR-T cell delivery were explored using orthotopic mouse HCC xenografts. CAR-T cell injection was performed locoregionally (through portal vein) and systemically (through tail vein). Compared to the systemic treatment, locoregional CAR-T therapy could better control the tumour growth, and was associated with improved liver function. In addition, increased percentage of tumour infiltrating CAR-T cells was observed in the locoregional therapy group, with those CAR-T cells gaining increased cytotoxicity, chemotaxis and less exhaustion phenotype. Furthermore, portal vein injection also exhibited a better tumour inhibition ability over tail vein injection on a metastatic model which simultaneously bore both orthotopic and extrahepatic tumour lesions. In the current study, we have demonstrated that locoregional administration of CAR-T cells is associated with increased tumour infiltration and better therapeutic efficacy. Moreover, our results provide insights that locoregional CAR-T therapy could also be employed to the late-stage patients with distant metastasis. Citation Format: Jue Wang, Bo Feng. Enhanced tumor infiltration and functionality of anti-GPC3 CAR-T cells in hepatocellular carcinoma through locoregional administration [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B035.