Work

CAR-T Cells Targeting HLA-G as Potent Therapeutic Strategy for EGFR Mutated and Overexpressed Oral Cancer

Year: 2022

Type: article

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-overactive 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. Funding Information: This study was reviewed and financially supported by the MOST in Taiwan (MOST 111-2314-B-039-047-; MOST 110-2314-B-039-052 and MOST 108-2320-B-039-046). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Human cross-sectional study was approved by the Institutional Review Board of CMUH (CMUH108-REC3-041). Written informed consent was obtained from each participant before enrolling in the study. The study was conducted in accordance with the principles of the Declaration of Helsinki. The experimental procedures for in vivo studies were approved by the Animal Protection Association of the Republic of China (ROC), and all animal protocols were approved by the CMU Institutional Animal Care and Utilization Committee (IACUC, CMUIACUC-2018-234). The number of animals used was approved by the ethical committee of the Ministry of Science and Technology (MOST) in Taiwan (MOST 110-2314-B-039-052 and MOST 108-2320-B-039-046). The experiments were performed such that the number of animals used was minimized. We confirm that all methods were performed in accordance with the relevant guidelines and regulations.

Source: iScience

DOI: 10.1016/j.isci.2023.106089