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.
Highlights
Discovery of p5370 years ago, several DNA viruses such as adenovirus, human Epstein–Barr virus, polyoma and SV40 were found to be able to cause tumors in humans and rodents [1]
The same 53kD protein was detected—and confirmed with peptide maps—in SV40-transformed cells and malignant cells that are not transformed by a virus, whereas decreased p53 levels were observed in uninfected normal cells
The scope of this review is to provide an update on the current knowledge of the expression of serum p53 antibodies (p53-Abs) (s-p53-Abs) and their prognostic value in cancer patients
Summary
70 years ago, several DNA viruses such as adenovirus, human Epstein–Barr virus, polyoma and SV40 were found to be able to cause tumors in humans and rodents [1]. These viral proteins—subsequently named tumor antigens (TA)—were recognized by the immune system and the different antibodies were found to target them [5] Given this scenario, in 1979, four different groups in England, the United States, and France nearly simultaneously discovered the p53 protein in normal and cancerous cells, testing the serum from animals with spontaneously derived or SV40 virus-induced tumors [6,7,8,9]. Malignant cells that were not transformed by any virus had increased levels of p53, suggesting that the SV40 tumor antigen, a well-known factor for the tumor initiation and progression, binds to p53 and raises its concentration above its normal levels in control healthy cells [10] These preliminary results paved the way for a vast number of studies on the role of cellular protein p53 in the cancer biology field, leading to the discovery that p53 mutations are the most common genetic alteration in human cancers. For a more comprehensive review on the different molecular interactions between p53-wt and immune molecules, please refer to Blagih et al [80]
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