Work

Targeting mutant p53-expressing tumours with a T cell receptor-like antibody specific for a wild-type antigen

Year: 2019

Type: article

Abstract: Accumulation of mutant p53 proteins is frequently found in a wide range of cancers. While conventional antibodies fail to target intracellular proteins, proteosomal degradation results in the presentation of p53-derived peptides on the tumour cell surface by class I molecules of the major histocompatibility complex (MHC). Elevated levels of such p53-derived peptide-MHCs on tumour cells potentially differentiate them from healthy tissues. Here, we report the engineering of an affinity-matured human antibody, P1C1TM, specific for the unmutated p53 125-134 peptide in complex with the HLA-A24 class I MHC molecule. We show that P1C1TM distinguishes between mutant and wild-type p53 expressing HLA-A24 + cells, and mediates antibody dependent cellular cytotoxicity of mutant p53 expressing cells in vitro. Furthermore, we show that cytotoxic PNU-159682-P1C1TM drug conjugates specifically inhibit growth of mutant p53 expressing cells in vitro and in vivo. Hence, p53-associated peptide-MHCs are attractive targets for the immunotherapy against mutant p53 expressing tumours.

Source: Nature Communications

DOI: 10.1038/s41467-019-13305-z

Authors: Lionel Low, Angeline Goh, Joanna Koh, Samantha Lim, Cheng-I Wang

Institutions: Agency for Science, Technology and Research, Singapore Immunology Network, Ngee Ann Polytechnic

Language: English

Topic: Monoclonal and Polyclonal Antibodies Research

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,200