Work

Bispecifics and CAR T cells that target intracellular cancer driver mutations

Year: 2021

Type: article

Abstract: The emergence of immunotherapy as an important tool in the fight against cancer takes advantage of the exquisite selectivity of antibodies.Until now successful targets, however, are limited to those on the cell surface, while most driver mutations occur in the genes encoding intracellular proteins.To overcome this limitation, antibodies can be engineered to target mutation derived neoantigens, peptides derived from mutant proteins that are presented on the cell surface by the Major Histocompatibility Complex Class I (MHC-I).In cases where both the wild-type (WT) and mutant peptide are presented, antibodies can be developed that selectively target the specific mutant peptide-HLA complex.We have selected antibody fragments by phage display that target mutant peptides derived from a tumour suppressor gene, specifically the R175H mutation in the protein p53 and from an oncogene (1), the R140Q mutation in isocitrate dehydrogenase 2 (IDH2).

Source: Acta Crystallographica Section A Foundations and Advances

DOI: 10.1107/s0108767321098780