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Comment
. 2021 Jun 3;6(1):219.
doi: 10.1038/s41392-021-00635-y.

The arsenal of TP53 mutants therapies: neoantigens and bispecific antibodies

Chang Yang  1 , Ge Lou  2 , Wei-Lin Jin  3
Affiliations
Comment

The arsenal of TP53 mutants therapies: neoantigens and bispecific antibodies

Chang Yang et al. Signal Transduct Target Ther. .
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Treatment strategies of p53 dysfunction. a Inhibition of the interaction between wild-type p53 and MDM2/MDM4: RG7112 and RG7338 are MDM2 inhibitors that hinder direct interaction between p53 and MDM2. ALRN-6924 is a dual MDM2/MDM4 inhibitor. RG7112, RG7338, and ALRN-6924 are currently undergoing clinical trials. b Restoration of wild-type p53 function: zinc metallochaperone-1 (ZMC1) restores the low Zn2+ affinity of mutant p53 induced by R175H mutation and enables mutant p53 to fold correctly. APR-246 is converted to methylene quinuclidinone (MQ), a Michael acceptor that reacts with cysteines in the p53 core domain, promoting wild-type p53 conformation. PK7088 binds to Y220C mutant, regulating tail protein stability and enhancing correct protein folding of mutant p53. c Bispecific antibody targeting mutant p53: H2-scDb binds to the p53 R175H peptide–HLA complex expressed on the tumor cell surface with one arm and to CD3 with the other arm, inducing T-cell activation and tumor killing
See this image and copyright information in PMC

Comment on

  • Targeting a neoantigen derived from a common TP53 mutation.
    Hsiue EH, Wright KM, Douglass J, Hwang MS, Mog BJ, Pearlman AH, Paul S, DiNapoli SR, Konig MF, Wang Q, Schaefer A, Miller MS, Skora AD, Azurmendi PA, Murphy MB, Liu Q, Watson E, Li Y, Pardoll DM, Bettegowda C, Papadopoulos N, Kinzler KW, Vogelstein B, Gabelli SB, Zhou S. Hsiue EH, et al. Science. 2021 Mar 5;371(6533):eabc8697. doi: 10.1126/science.abc8697. Epub 2021 Mar 1. Science. 2021. PMID: 33649166 Free PMC article.

References

    1. Hsiue EH-C, et al. Targeting a neoantigen derived from a common TP53 mutation. Science. 2021;371:eabc8697. doi: 10.1126/science.abc8697. - DOI - PMC - PubMed
    1. Duffy, M. J., Synnott, N. C., O’Grady, S. & Crown, J. Targeting p53 for the treatment of cancer. Semin. Cancer Biol. (in the press). - PubMed
    1. Douglass J, et al. Bispecific antibodies targeting mutant RAS neoantigens. Sci. Immunol. 2021;6:eabd5515. doi: 10.1126/sciimmunol.abd5515. - DOI - PMC - PubMed
    1. Paul S, et al. TCR beta chain-directed bispecific antibodies for the treatment of T-cell cancers. Sci. Transl. Med. 2021;13:eabd3595. doi: 10.1126/scitranslmed.abd3595. - DOI - PMC - PubMed
    1. Weidanz J. Targeting cancer with bispecific antibodies. Science. 2021;371:996. doi: 10.1126/science.abg5568. - DOI - PubMed

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