Human T cells engineered with an HLA-A2-restricted murine T-cell receptor targeting glypican 3 effectively control human hepatocellular carcinoma in mice.

ABSTRACT:

Background and aims

Glypican-3 (GPC3) is a promising target for T-cell therapy in HCC. While chimeric antigen receptor (CAR) T cells targeting GPC3 have demonstrated therapeutic efficacy, their effectiveness is limited by challenges such as low persistence and shedding of surface GPC3. Natural T-cell receptors (TCRs) may serve as an alternative, though identifying GPC3-specific TCRs within the endogenous repertoire is difficult.

Approach and results

We immunized human leucocyte antigen-A2 (HLA-A2) transgenic mice with an adenovirus expressing human GPC3, identifying a panel of TCRs that recognize the GPC3(522-530) epitope. We cloned 3 murine GPC3-TCRs (TCR-A, TCR-B, and TCR-C) and engineered primary human T cells (TCR-T). TCR-T cells effectively recognized GPC3 + HLA-A2 + hu

SUBMITTER: Vercher E 

PROVIDER: S-EPMC12266797 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature