Tgfβ-counteracting AB-CARM for tumoricidal immunological hubs in liver cancer

Overview

AB-CARM is an innovative therapeutic approach developed by SynHealer, aimed at combating liver cancer by harnessing the power of engineered macrophages. This technology focuses on counteracting TGFβ, a key factor in tumor microenvironment (TME) immunosuppression. By leveraging the antigen presentation capabilities of tumor-associated macrophages (TAM), AB-CARM enhances the immunogenicity of tumors. The engineered CAR-macrophages are designed to recognize and target liver cancer cells, activate innate immune responses, and present antigens to surrounding T-cells, effectively forming tumoricidal immunological hubs that combat cancer cell heterogeneity.

Technical specifications

• CAR-macrophages: Engineered to secrete TGFβ-blocking antibody fragments, enhancing T-cell cancer-killing abilities.
• TGFβ-blocking: Facilitates the reprogramming of macrophages into active immune participants.
• LNP delivery system: Utilizes PPZ-based lipid nanoparticles for the transduction of macrophages.
• Target specificity: Recognizes liver cancer cells expressing GPC3, validated through in vitro and in vivo studies.
• Immunological hub formation: Proven ability to reinvigorate T-cells and macrophages, resisting the immunosuppressive TME.

Technology readiness level

Currently at TRL 3, AB-CARM has demonstrated promising results in preclinical settings, including pilot data supporting its efficacy in targeting liver cancer cells and enhancing immune responses. Future validation steps involve forming tumoricidal immunological hubs in immune-competent mouse models and defining TCR/BCR clonality in patient tumor slice cultures.