Targeting public neoantigens for cancer immunotherapy

Alexander H Pearlman; Michael S Hwang; Maximilian F Konig; Emily Han-Chung Hsiue; Jacqueline Douglass; Sarah R DiNapoli; Brian J Mog; Chetan Bettegowda; Drew M Pardoll; Sandra B Gabelli; Nicholas Papadopoulos; Kenneth W Kinzler; Bert Vogelstein; Shibin Zhou

doi:10.1038/s43018-021-00210-y

Targeting public neoantigens for cancer immunotherapy

Nat Cancer. 2021 May;2(5):487-497. doi: 10.1038/s43018-021-00210-y. Epub 2021 May 17.

Authors

Alexander H Pearlman^{1

2

3}, Michael S Hwang^{1

2

3

4}, Maximilian F Konig^{1

2

3

5}, Emily Han-Chung Hsiue^{1

2

3}, Jacqueline Douglass^{1

2

3}, Sarah R DiNapoli^{1

2

3}, Brian J Mog^{1

2

3

6}, Chetan Bettegowda^{1

2

7

8}, Drew M Pardoll^{8

9}, Sandra B Gabelli^{8

10

11}, Nicholas Papadopoulos^{1

2

9

12

13}, Kenneth W Kinzler^{1

2

8

9

13}, Bert Vogelstein^{1

2

3

8

9

12

13}, Shibin Zhou^{14

15

16

17}

Affiliations

¹ Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Howard Hughes Medical Institute, Chevy Chase, MD, USA.
⁴ Genentech, Inc., South San Francisco, CA, USA.
⁵ Division of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁷ Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
¹⁰ Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹² Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹³ Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁴ Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. sbzhou@jhmi.edu.
¹⁵ Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. sbzhou@jhmi.edu.
¹⁶ Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. sbzhou@jhmi.edu.
¹⁷ Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. sbzhou@jhmi.edu.

Abstract

Several current immunotherapy approaches target private neoantigens derived from mutations that are unique to individual patients' tumors. However, immunotherapeutic agents can also be developed against public neoantigens derived from recurrent mutations in cancer driver genes. The latter approaches target proteins that are indispensable for tumor growth, and each therapeutic agent can be applied to numerous patients. Here we review the opportunities and challenges involved in the identification of suitable public neoantigen targets and the development of therapeutic agents targeting them.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Antigens, Neoplasm* / genetics
Humans
Immunologic Factors / therapeutic use
Immunotherapy
Mutation
Neoplasms* / therapy
Oncogenes

Substances

Antigens, Neoplasm
Immunologic Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding