Abstract 6112: Supercharging anti-tumor immunity in hepatocellular carcinoma with PH102: A CAR T-cell-based platform

Abstract Hepatocellular carcinoma (HCC) is the 5th leading cause of cancer death in the US among males (7th among females) and remains a major cause of cancer-related death worldwide with especially high prevalence in South Texas (12 per 100,000). HCC is caused by HBV/HCV infections, metabolic dysfunction, and alcoholic steatohepatitis. The majority of HCC patients present clinically with advanced disease and are treated with ineffective systemic therapies including chemotherapy and/or immune checkpoint inhibitors. There’s a pressing need for an innovative, curative immunotherapy for advanced, unresectable HCC for whom liver transplantation is not possible. The tumor immune microenvironment (TiME) of HCC is a complex milieu of tumor, stromal, and immune cells that interact to modulate tumor growth. We designed a first-in-class precision immunotherapy approach based on established chimeric antigen receptor (CAR) T-cell technology that packages three different targeting approaches into a comprehensive cell-based platform to rebuild the anti-tumor TiME. PH102 is a CAR T-cell-based therapy targeting GPC3 (tumor antigen highly expressed in HCC but not healthy hepatocytes or normal tissues) while co-expressing factors A and B, immune signaling molecules that supercharge anti-tumor immune cells. We have shown exceptional preclinical safety and efficacy of PH102 in multiple solid tumor animal models including a tumor implantation model and a hydrodynamic tail vein injection (HTVI) murine model of in situ HCC. PH102 has been demonstrated to significantly improve probability of survival in mice carrying advanced HCC tumors, eliciting powerful elimination of advanced tumors via immune killing of cancer cells. Immunomodulatory factors A and B synergize to induce increased infiltration, expansion, and activation of cytotoxic T-cells, tissue resident memory T-cells, conventional NK cells, liver resident NK cells, and dendritic cells within the TiME. Altogether, PH102’s triple-hit approach induces a potent and durable anti-tumor, immune-triad-mediated killing program alongside creating long-term immune memory that persists long after CAR T-cell exhaustion. PH102 is warranted to be translated into a phase I/II HCC trial following final preclinical safety and efficacy validation. Citation Format: Vincent Truong Pham, Shaozi Fu, Victoria Sanchez, Ya-Guang Liu, Kasie Liu, Araceli Bernal, LuZhe Sun, Gang Huang. Supercharging anti-tumor immunity in hepatocellular carcinoma with PH102: A CAR T-cell-based platform [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 6112.