CAR-T cells targeting HLA-G as potent therapeutic strategy for EGFR-mutated and overexpressed oral cancer

Yu-Chuan Lin; Chun-Hung Hua; Hsin-Man Lu; Shi-Wei Huang; Yeh Chen; Ming-Hsui Tsai; Fang-Yu Lin; Peter Canoll; Shao-Chih Chiu; Wei-Hua Huang; Der-Yang Cho; Chia-Ing Jan

doi:10.1016/j.isci.2023.106089

CAR-T cells targeting HLA-G as potent therapeutic strategy for EGFR-mutated and overexpressed oral cancer

iScience. 2023 Jan 31;26(3):106089. doi: 10.1016/j.isci.2023.106089. eCollection 2023 Mar 17.

Authors

Yu-Chuan Lin^{1

2}, Chun-Hung Hua³, Hsin-Man Lu⁴, Shi-Wei Huang^{2

5}, Yeh Chen^{5

6}, Ming-Hsui Tsai³, Fang-Yu Lin², Peter Canoll⁷, Shao-Chih Chiu^{1

2

6}, Wei-Hua Huang^{8

9}, Der-Yang Cho^{1

2

6

10}, Chia-Ing Jan¹¹

Affiliations

¹ Drug Development Center, China Medical University, Taichung 404, Taiwan.
² Translational Cell Therapy Center, China Medical University Hospital, No. 2, Yude Road, North District, Taichung 404, Taiwan.
³ Department of Otorhinolaryngology, China Medical University Hospital, Taichung 404, Taiwan.
⁴ Department of Psychology, Asia University, Taichung 404, Taiwan.
⁵ Institute of New Drug Development, China Medical University, Taichung 404, Taiwan.
⁶ Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
⁷ Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
⁸ Dr. Jean Landsborough Memorial Hospice Ward, Changhua Christian Hospital, Changhua 500, Taiwan.
⁹ Department of Nursing, Central Taiwan University of Science and Technology, Taichung 406, Taiwan.
¹⁰ Department of Neurosurgery, China Medical University Hospital, Taichung 404, Taiwan.
¹¹ Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignancy in the world. Recently, scientists have focused on therapeutic strategies to determine the regulation of tumors and design molecules for specific targets. Some studies have demonstrated the clinical significance of human leukocyte antigen G (HLA-G) in malignancy and NLR family pyrin domain-containing 3 (NLRP3) inflammasome in promoting tumorigenesis in OSCC. This is the first study to investigate whether aberrant epidermal growth factor receptor (EGFR) induces HLA-G expression through NLRP3 inflammasome-mediated IL-1β secretion in OSCC. Our results showed that the upregulation of NLRP3 inflammasome leads to abundant HLA-G in the cytoplasm and cell membrane of FaDu cells. In addition, we also generated anti-HLA-G chimeric antigen receptor (CAR)-T cells and provided evidence for their effects in EGFR-mutated and overexpressed oral cancer. Our results may be integrated with OSCC patient data to translate basic research into clinical significance and may lead to novel EGFR-aberrant OSCC treatment.

Keywords: Cancer; Cell biology; Immunology; Molecular biology.