Mutant p53 as an Antigen in Cancer Immunotherapy

International Journal of Molecular Sciences

Alberto D’Angelo¹  Daniele Generali²  KenH. Young³  Xu Wang⁴  Navid Sobhani⁴  Yong Li⁴ 

[1] Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK;Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada Di Fiume 447, 34149 Trieste, Italy;Department of Pathology, Duke University School of Medicine, Durham, NC 27708, USA;Section of Epidemiology and Population Science, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA;

关键词: p53;    serum antibodies;    tumor suppressor;    immunoncology;    cancer;   

DOI  :  10.3390/ijms21114087

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown