Design of immunogens to present a tumor-specific cryptic epitope.

ABSTRACT: In many cancers, the epidermal growth factor receptor (EGFR) gene is amplified, mutated, or both. The monoclonal antibody mAb806 binds selectively to cancer cells that overexpress EGFR or express the truncated mutant EGFRvIII, but not to normal cells. This suggests that a promising avenue for developing cancer vaccines may be to design immunogens that elicit mAb806-like antibodies. In this study, we designed immunogens that present the mAb806-binding epitope in the same conformation as in overexpressed or truncated EGFR. We first used molecular dynamics simulations to identify conformations of EGFR in which the residues of the mAb806-binding epitope are accessible. We then designed immunogens by substituting that epitope in place of a structurally similar loop in a different protein and ge

SUBMITTER: Xu H 

PROVIDER: S-EPMC11965450 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature