Mutant p53 as an Antigen in Cancer Immunotherapy

Navid Sobhani, Alberto D'Angelo, Xu Wang, Ken H Young, Daniele Generali, Yong Li

Research output: Contribution to journalReview article

Abstract

The p53 tumor suppressor plays a pivotal role in cancer and infectious disease. Many oncology treatments are now calling on immunotherapy approaches, and scores of studies have investigated the role of p53 antibodies in cancer diagnosis and therapy. This review summarizes the current knowledge from the preliminary evidence that suggests a potential role of p53 as an antigen in the adaptive immune response and as a key monitor of the innate immune system, thereby speculating on the idea that mutant p53 antigens serve as a druggable targets in immunotherapy. Except in a few cases, the vast majority of published work on p53 antibodies in cancer patients use wild-type p53 as the antigen to detect these antibodies and it is unclear whether they can recognize p53 mutants carried by cancer patients at all. We envision that an antibody targeting a specific mutant p53 will be effective therapeutically against a cancer carrying the exact same mutant p53. To corroborate such a possibility, a recent study showed that a T cell receptor-like (TCLR) antibody, initially made for a wild-type antigen, was capable of discriminating between mutant p53 and wild-type p53, specifically killing more cancer cells expressing mutant p53 than wild-type p53 in vitro and inhibiting the tumour growth of mice injected with mutant p53 cancer cells than mice with wild-type p53 cancer cells. Thus, novel antibodies targeting mutant p53, but not the wild-type isoform, should be pursued in preclinical and clinical studies.

Original languageEnglish
Article number4087
Pages (from-to)1-21
Number of pages21
JournalInternational Journal of Molecular Sciences
Volume21
Issue number11
DOIs
Publication statusPublished - 8 Jun 2020

Keywords

  • Cancer
  • Immunoncology
  • P53
  • Serum antibodies
  • Tumor suppressor

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Sobhani, N., D'Angelo, A., Wang, X., Young, K. H., Generali, D., & Li, Y. (2020). Mutant p53 as an Antigen in Cancer Immunotherapy. International Journal of Molecular Sciences, 21(11), 1-21. [4087]. https://doi.org/10.3390/ijms21114087