Human VH-antibody-based CAR T cells targeting folate receptor-alpha show enhanced persistence and reduced T-cell exhaustion against ovarian cancer - PubMed
3 hours ago
- #CAR T-cell therapy
- #Ovarian cancer
- #Folate receptor-alpha
- Folate receptor-alpha (FOLR1) is highly expressed in ovarian cancer and is a target for adoptive cell therapy.
- A second-generation FOLR1-specific CAR was developed using a fully human VH-only antibody and compared with a MOv19-derived scFV CAR.
- Both VH-based and scFV-based FOLR1 CAR T cells showed potent cytotoxicity against FOLR1-positive ovarian cancer cells.
- FOLR1-VH CAR T cells exhibited lower activation and cytokine release initially, with reduced exhaustion markers like PD-1 and LAG-3.
- FOLR1-VH CAR T cells maintained a central-memory phenotype and demonstrated superior persistence and tumor control in repeated rechallenge assays.
- Both CAR formats achieved similar cytotoxicity in 3D spheroid models.
- Human FOLR1-VH CAR T cells showed potent antitumor activity with reduced exhaustion and enhanced persistence, highlighting the VH domain's potential for next-generation CAR T-cell therapies.