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Comment
. 2021 May 10;39(5):604-606.
doi: 10.1016/j.ccell.2021.04.010.

Arming "old guards" with "new dual-targeting weapons"

Lawrence G Lum  1 , Jogender Tushir-Singh  2
Affiliations
Comment

Arming "old guards" with "new dual-targeting weapons"

Lawrence G Lum et al. Cancer Cell. .

Abstract

The long-held paradigm that tumor suppressors are un-targetable in cancer therapy is challenged by a study published in Science. This recent work elegantly describes and characterizes a p53 mutant peptide-selective TCR-mimic antibody and its co-targeting T cell-activating bispecific antibody to eliminate neoantigen-expressing tumors.

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Conflict of interest statement

Declaration of interest J.T.-S. is an Early Career Investigator (ECI) of DoD Ovarian Cancer Academy (OC180412) and is also supported by NCI (R01CA233752) and DoD Breast Cancer Research Program (BCRP) funding (BC170197). L.G.L is supported in part by NCI (R01CA182526). L.G.L. is co-founder of Transtarget Inc. and serves on the SAB for Rapa Therapeutics.

Figures

Figure 1.
Figure 1.. Neoantigen-targeting T cell engaging bispecific strategies for various cancers
Enriched pan-cancer and cancer-specific p53 (and other tumor suppressors) mutations are sources of neoantigens, which can be selectively targeted using TCR mimic antibodies. Either CAR-T cells expressing TCR mimic antibodies or a particular bispecific format antibody co-targeting antigen on T cell and neoantigens from tumor cells could not only boost effective anti-tumor cytotoxicity but also shields the wild-type p53 antigen-presenting cells from attack. *, the % p53 mutation frequency is according to cBioportal database (Kandoth et al., 2013; Robinson et al., 2017). #, Suggested neo-antigenic peptides are hypothetical, based on the study published in Science and indicated cancer-specific p53 mutation frequency.
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

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