Epidermal growth factor receptor (EGFR) mutation-derived neoantigen (EGFR neoantigen)

Epidermal growth factor receptor (EGFR) mutation-derived neoantigens are highly specific tumor antigens generated by somatic mutations in the EGFR gene, such as the EGFRvIII deletion or point mutations like L858R and T790M (PubMed: 28456428). These mutations produce novel amino acid sequences that are processed and presented as peptides on the cell surface by Major Histocompatibility Complex (MHC) molecules, primarily in indications like glioblastoma and non-small cell lung cancer (NSCLC) (Nature Reviews Cancer, 2019). Unlike wild-type EGFR, which is widely expressed in epithelial tissues, these neoantigens are restricted to malignant cells, offering a therapeutic window for precision immunotherapies including cancer vaccines, TCR-engineered T cells (TCR-T), and chimeric antigen receptor (CAR) T cells (Lancet Oncology, 2017). Drugs like Rindopepimut and VBI-1901 have been developed to elicit immune responses against these targets, though clinical success has been tempered by challenges such as intratumoral heterogeneity and antigen escape (Journal of Clinical Oncology, 2019). The biological function of the parent receptor involves driving oncogenic signaling pathways, while the neoantigen itself serves as a molecular flag for immune recognition. Effective targeting requires precise patient selection based on both mutation status and HLA-type compatibility (Cancer Discovery, 2017).

Other names

EGFRvIIIEGFR neoepitopeEGFR mutant peptideEpidermal growth factor receptor variant IIIEGFR L858R neoantigenEGFR T790M neoantigen

Induction of a cytotoxic T-lymphocyte response or direct CAR-T binding to eliminate tumor cells presenting mutant EGFR peptides on MHC molecules.