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Targeting Alpha-Fetoprotein (AFP)-MHC Complex with CAR T-Cell Therapy for Liver Cancer.
Hong Liu1, Yiyang Xu1, Jingyi Xiang1
1Eureka Therapeutics Inc., Emeryville, California.
Summary
Chimeric antigen receptor (CAR) T-cell therapy can target intracellular liver cancer antigens. This study shows AFP-CAR T cells effectively eliminate tumors expressing the alpha-fetoprotein (AFP) peptide-MHC complex.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Most tumor antigens are intracellular or secreted, limiting conventional CAR T-cell therapy.
- Peptide-MHC complexes on tumor surfaces present intracellular antigens for potential targeting.
Purpose of the Study:
- To investigate if peptide-MHC complexes can be targeted by CAR T-cell therapy.
- To evaluate alpha-fetoprotein (AFP) as a target for liver cancer immunotherapy.
Main Methods:
- Generated a chimeric antigen receptor (AFP-CAR) targeting the AFP peptide-MHC complex (AFP158-166/HLA-A*02:01).
- Tested AFP-CAR T-cell activity against liver cancer cells in vitro and in vivo models.
Main Results:
- AFP-CAR T cells selectively killed HLA-A*02:01+/AFP+ liver cancer cells.
- Demonstrated significant tumor regression and growth inhibition in mouse models (Hep G2, SK-HEP-1).
- Confirmed robust antitumor activity in an established liver cancer xenograft model.
Conclusions:
- CAR T-cell immunotherapy targeting intracellular/secreted tumor antigens is effective.
- This approach broadens targets for solid tumor immunotherapy, offering a new strategy for liver cancer treatment.
