Structure-based design of Inmunotherapies
We are exploiting the genetic aberrations that drive tumorigenesis to design personalized therapeutics by targeting the commonly mutated cancer driver genes which encode intracellular proteins, p53, IDH2, RAS.
Mutated protein products derived from cancer driver genes can be processed and presented as peptides (neoantigens) by human leukocyte antigen (HLA) molecules. We are selecting T cell receptor-mimic (TCRm) antibodies that can distinguish single amino acid differences between pHLA complexes derived from the protein products of cancer driver hotspot mutations and those from the native protein. TCRm antibodies can be grafted into bispecific T cell engaging antibodies that bridge the T cell receptor to the pHLA or convert to CAR T cell therapeutic formats. We are interested on decoding the rules of TCR and antibody recognition of neontigens-MHC such as how to discriminate wt vs neoantigen while maintaining specificity without cross reactivity to exploit for structure-guided engineered therapeutics.