IMMUNOLOGY2026™ Conference Recordings For Attendees-Structural Insights and Immunogenic Enhancement of KRAS Neoantigen Recognition by TCRs in Cancer Immunotherapy

Structural Insights and Immunogenic Enhancement of KRAS Neoantigen Recognition by TCRs in Cancer Immunotherapy

Video Transcription

Video Summary

The talk describes structural studies of KRAS G12D neoantigen recognition by T cell receptors (TCRs) for cancer immunotherapy. KRAS is a common but historically “undruggable” cancer driver, so the lab targets KRAS mutant peptides presented by MHC on tumor cells. The speaker compared 9-mer and 10-mer KRAS G12D peptides and found that both are stable, but only the 10-mer is strongly recognized by TCRs because it is more bulged, dynamic, and exposed, while the 9-mer is flatter and buried. Crystal structures showed that several TCRs induce a major peptide rearrangement, flipping the mutated aspartate downward into the MHC groove. The lab is testing peptide backbone modifications to pre-stabilize the TCR-favored conformation. They also studied HLA restriction, showing that one TCR clinical candidate can recognize both HLA-A11 and the closely related HLA-A3-A2 allele, expanding potential patient coverage.

Meta Tag

Date April 17, 2026 1:45 PM - 2:00 PM

Room 104AB

Session Targeting Adaptive Immune Responses against Cancer and Other Pathologies

Speaker Bassant Eldaly

Track Vaccines and Immunotherapy (VAC)

Year 2026

Keywords

KRAS G12D

neoantigen recognition

T cell receptor

MHC peptide presentation

cancer immunotherapy

April 17, 2026 1:45 PM - 2:00 PM

104AB

Targeting Adaptive Immune Responses against Cancer and Other Pathologies

Bassant Eldaly

Vaccines and Immunotherapy (VAC)

2026