Precision immunointerception of EGFR-driven tumorigenesis for lung cancer prevention

Frontiers in Immunology

Immunology

Ming You¹  Jing Pan¹  Qi Zhang¹  Yian Wang¹  Donghai Xiong¹  Shizuko Sei²  Robert H. Shoemaker²  Bryon Johnson³  Katie Palen³ 

[1] Center for Cancer Prevention, Houston Methodist Cancer Center, Houston Methodist Research Institute, Houston, TX, United States;Cancer Center and Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, United States;Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, United States;Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, United States;

关键词: precision immunoprevention;    immunointerception;    EGFR mutation;    peptide vaccine;    MHC class II;    T cell;   

DOI  :  10.3389/fimmu.2023.1036563

 received in 2022-09-04, accepted in 2023-01-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Epidermal growth factor receptor (EGFR) mutations occur in about 50% of lung adenocarcinomas in Asia and about 15% in the US. EGFR mutation-specific inhibitors have been developed and made significant contributions to controlling EGFR mutated non-small cell lung cancer. However, resistance frequently develops within 1 to 2 years due to acquired mutations. No effective approaches that target mutant EGFR have been developed to treat relapse following tyrosine kinase inhibitor (TKI) treatment. Vaccination against mutant EGFR is one area of active exploration. In this study, we identified immunogenic epitopes for the common EGFR mutations in humans and formulated a multi-peptide vaccine (Emut Vax) targeting the EGFR L858R, T790M, and Del19 mutations. The efficacy of the Emut Vax was evaluated in both syngeneic and genetic engineered EGFR mutation-driven murine lung tumor models with prophylactic settings, where the vaccinations were given before the onset of the tumor induction. The multi-peptide Emut Vax effectively prevented the onset of EGFR mutation-driven lung tumorigenesis in both syngeneic and genetically engineered mouse models (GEMMs). Flow cytometry and single-cell RNA sequencing were conducted to investigate the impact of Emut Vax on immune modulation. Emut Vax significantly enhanced Th1 responses in the tumor microenvironment and decreased suppressive Tregs to enhance anti-tumor efficacy. Our results show that multi-peptide Emut Vax is effective in preventing common EGFR mutation-driven lung tumorigenesis, and the vaccine elicits broad immune responses that are not limited to anti-tumor Th1 response.

【 授权许可】

Unknown   
Copyright © 2023 Pan, Xiong, Zhang, Palen, Shoemaker, Johnson, Sei, Wang and You