Unknown

Dataset Information

0

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


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 p53125-134 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.

SUBMITTER: Low L 

PROVIDER: S-EPMC6879612 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Low Lionel L   Goh Angeline A   Koh Joanna J   Lim Samantha S   Wang Cheng-I CI  

Nature communications 20191126 1


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 hum  ...[more]

Similar Datasets

| S-EPMC3109573 | biostudies-literature
| S-EPMC7750800 | biostudies-literature
| S-EPMC3260009 | biostudies-literature
| S-EPMC6756012 | biostudies-literature
| S-EPMC6147029 | biostudies-literature
| S-EPMC6103823 | biostudies-literature
| S-EPMC3268447 | biostudies-literature
| S-EPMC3377636 | biostudies-literature
| S-EPMC4670040 | biostudies-literature
| S-EPMC6941974 | biostudies-literature