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Updated: Aug 8, 2025
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Precision immunointerception of EGFR-driven tumorigenesis for lung cancer prevention
Jing Pan1,2, Donghai Xiong1,2, Qi Zhang1,2
1Center for Cancer Prevention, Houston Methodist Cancer Center, Houston Methodist Research Institute, Houston, TX, United States.
Abstract:
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.
Insights
A novel multi-peptide vaccine targeting common epidermal growth factor receptor (EGFR) mutations effectively prevented lung cancer development in preclinical models. This vaccine enhanced anti-tumor immune responses, showing promise for preventing EGFR-mutated lung cancer.
Area of Science:
- Oncology
- Immunology
- Vaccinology
Background:
- Epidermal growth factor receptor (EGFR) mutations drive lung adenocarcinoma, particularly in Asia.
- While EGFR inhibitors are effective, acquired resistance and relapse are significant clinical challenges.
- Targeted therapies for relapsed EGFR-mutated lung cancer remain limited, necessitating novel treatment strategies.
Purpose of the Study:
- To develop and evaluate a multi-peptide vaccine (Emut Vax) targeting common EGFR mutations (L858R, T790M, Del19).
- To assess the prophylactic efficacy of Emut Vax in preventing EGFR mutation-driven lung tumorigenesis.
- To investigate the immunomodulatory effects of Emut Vax in the tumor microenvironment.
Main Methods:
- Identification of immunogenic epitopes for common EGFR mutations.
- Formulation of a multi-peptide vaccine (Emut Vax).
- Evaluation of prophylactic efficacy in syngeneic and genetically engineered mouse models (GEMMs).
- Analysis of immune responses using flow cytometry and single-cell RNA sequencing.
Main Results:
- Emut Vax demonstrated significant efficacy in preventing lung tumorigenesis in both syngeneic and GEMM models.
- Vaccination led to enhanced Th1 immune responses within the tumor microenvironment.
- Emut Vax reduced the population of suppressive regulatory T cells (Tregs), thereby enhancing anti-tumor immunity.
- The vaccine elicited broad immune responses beyond just Th1-mediated anti-tumor activity.
Conclusions:
- Multi-peptide Emut Vax is a promising strategy for preventing EGFR mutation-driven lung tumorigenesis.
- The vaccine effectively modulates the immune system to create an anti-tumor environment.
- Emut Vax warrants further investigation as a prophylactic intervention for individuals at risk of EGFR-mutated lung cancer.
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