A peptide antigen derived from EGFR T790M is immunogenic in non‑small cell lung cancer

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Lung cancer is a leading cause of cancer deaths globally.
• Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective against EGFR-mutated non-small cell lung cancer (NSCLC).
• Acquired resistance to EGFR-TKIs, often due to the EGFR T790M mutation, necessitates novel therapeutic approaches.

Purpose of the Study:

• To evaluate the immunogenicity of an antigen derived from the EGFR T790M mutation.
• To explore new immunotherapy targets for NSCLC patients with acquired resistance to EGFR-TKIs.

Main Methods:

• Peptides derived from EGFR T790M were selected for binding to HLA-A*02:01 using BIMAS.
• T790M-A peptide-specific cytotoxic T lymphocytes (CTLs) were induced from peripheral blood mononuclear cells (PBMCs).
• Interferon-γ (IFN-γ) enzyme-linked immuno spot (ELISPOT) assays and cytotoxicity assays were used to assess CTL reactivity.

Main Results:

• EGFR T790M-derived peptides were identified that bind to HLA-A*02:01.
• T790M-A peptide-specific CTLs were successfully induced and demonstrated reactivity against NSCLC cells expressing the T790M mutation and HLA-A2.
• The induced CTL line exhibited peptide-specific cytotoxicity against T790M-positive NSCLC cells.

Conclusions:

• The EGFR T790M mutation-derived antigen shows promise as a novel target for cancer immunotherapy.
• Targeting this mutation-specific antigen could overcome acquired resistance to EGFR-TKIs in NSCLC.
• Further research into this EGFR T790M-derived antigen may lead to new immunotherapeutic strategies for lung cancer.