A platform for T-cell receptor mimic antibody generation modeled using pHLA-A*11:01 KRAS G12D

ABSTRACT This Phase II proposal is an ambitious advancement for precision oncology, focusing on the discovery and validation of T cell receptor mimic antibodies (TCRms) targeting mutation-associated neoantigens (MANAs) specific to KRAS mutations. More specifically the KRASG12D mutation in the HLA-A*11:01 allele. This project, rooted in the innovative 'Epivolve' technology, aims to enhance the specificity and efficacy of immunotherapies by developing novel antibodies that can distinguish between mutant and wild-type KRAS peptides. The significance of this research lies in its potential to overcome the longstanding challenge of targeting intracellular oncogenic proteins, which are otherwise inaccessible to conventional therapies. Upon successful completion, this strategy could transform the therapeutic landscape for numerous cancers characterized by KRAS mutations and other neoantigens, offering highly targeted treatments with potentially fewer off-target effects and significantly improved patient outcomes in the oncology field.