New Publication in ACS Omega

We are pleased to announce that our paper, "Computational Design of a TCR-Based Bispecific Engager Targeting Cancerous KRAS G12V Mutations," has been published in ACS Omega, a peer-reviewed journal of the American Chemical Society.

Authors: Nisarg Shah, Gargi Sharma, Vihaan Patel, Melinda Wu, Anishreddy Mummadi, Anya Taneja, Moksh Shah, Gia Bao Le, Madhav Krishna, and Harman Brah

Affiliation: Department of Chemistry and Biochemistry, Aspiring Scholars Directed Research Program (ASDRP)

Summary

KRAS G12V is among the most common oncogenic mutations and currently lacks any FDA-approved targeted therapy. In this study, we used a fully computational approach to design two novel TCR-based bispecific T-cell engagers (TCR-BiTEs) that pair a T-cell receptor specific to the KRAS G12V neoantigen with an anti-CD3 single-chain variable fragment. Each construct targets a different HLA allele (HLA-A03:01 and HLA-A11:01), broadening potential patient coverage. We validated our designs using AlphaFold2 structural prediction, free energy estimation, and molecular dynamics simulations, establishing a computational pipeline that can be extended to other neoantigen targets beyond KRAS G12V.

The article is published open access under a CC-BY-NC-ND 4.0 license and can be read in full here: https://pubs.acs.org/doi/10.1021/acsomega.5c10229