Targeting a neoantigen derived from a common TP53 mutation-Reference-Cited by-同舟云学术

Targeting a neoantigen derived from a common TP53 mutation

Published:2021-03-05 Issue:6533 Volume:371 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Hsiue Emily Han-Chung¹²³^ORCID,Wright Katharine M.²⁴⁵^ORCID,Douglass Jacqueline¹²³^ORCID,Hwang Michael S.¹²³,Mog Brian J.¹²³⁶^ORCID,Pearlman Alexander H.¹²³^ORCID,Paul Suman¹²³⁷^ORCID,DiNapoli Sarah R.¹²³^ORCID,Konig Maximilian F.¹²³⁸^ORCID,Wang Qing¹²⁹^ORCID,Schaefer Annika¹²³^ORCID,Miller Michelle S.²⁴⁵^ORCID,Skora Andrew D.¹²^ORCID,Azurmendi P. Aitana²⁴⁵^ORCID,Murphy Michael B.¹⁰^ORCID,Liu Qiang¹²³^ORCID,Watson Evangeline¹²³,Li Yana⁴^ORCID,Pardoll Drew M.⁵⁷^ORCID,Bettegowda Chetan¹³¹¹^ORCID,Papadopoulos Nickolas¹³⁵¹²^ORCID,Kinzler Kenneth W.¹³⁵^ORCID,Vogelstein Bert¹²³⁵¹²^ORCID,Gabelli Sandra B.⁴⁷¹³^ORCID,Zhou Shibin¹³⁵^ORCID

Affiliation:

1. Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

2. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

3. Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

4. Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

5. Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA.

6. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.

7. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

8. Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.

9. Complete Omics, Baltimore, MD 21227, USA.

10. Cytiva, Marlborough, MA 01752, USA.

11. Department of Neurosurgery, Johns Hopkins University School of Medicine, MD 21205, USA.

12. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

13. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Turning a tumor suppressor into a target Tumor-suppressor genes such as TP53 (tumor protein P53) play key roles in the pathogenesis of cancer but, unfortunately, they are difficult to target because they do not create an overactive protein that can be inhibited with a drug. Hsiue et al. discovered a way to target a cancer-associated mutant form of the p53 protein using the body's own immune system (see the Perspective by Weidanz). The authors identified a distinct fragment of this mutant protein, characterized the structural basis for its presentation to T cells, and designed a bispecific antibody to stimulate T cell killing of p53-mutant cancer cells. Science , this issue p. eabc8697 ; see also p. 996

Funder

National Institutes of Health

Howard Hughes Medical Institute

National Cancer Institute

Commonwealth Fund

Lustgarten Foundation

Virginia and D.K. Ludwig Fund for Cancer Research

Mark Foundation For Cancer Research

Bloomberg Philanthropies

The Bloomberg~Kimmel Institute for Cancer Immunotherapy

Burroughs Wellcome Fund

Society for Immunotherapy of Cancer