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.
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Data availability
Data for The Cancer Genome Atlas mutation frequencies used in the analyses presented in Fig. 3 and Table 2 are available from the National Cancer Institute Genomics Data Commons (https://gdc.cancer.gov/). Data for the HLA frequencies used in the analyses presented in Tables 1 and 2 and Supplementary Table 1 are available from the Allele Frequency Net Database (http://www.allelefrequencies.net/) and National Marrow Donor Program (https://bioinformatics.bethematchclinical.org/hla-resources/haplotype-frequencies/high-resolution-hla-alleles-and-haplotypes-in-the-us-population/). Data for cancer incidence used in the analyses presented in Fig. 3 and Table 2 are available from the National Cancer Institute Surveillance, Epidemiology, and End Results Program (https://seer.cancer.gov/statfacts/html/common.html). Data for ethnicity representation in the United States used in the analyses presented in Tables 1 and 2 and Supplementary Table 1 are available from the United States Census Bureau (https://www.census.gov/quickfacts/fact/table/US/PST045219).
Change history
29 July 2021
A Correction to this paper has been published: https://doi.org/10.1038/s43018-021-00246-0
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Acknowledgements
We thank J. Cohen, M. Miller, S. Paul and K. Wright for insightful discussions, and E. Cook for assistance with Figs. 1 and 2. This work was supported by the Virginia and D. K. Ludwig Fund for Cancer Research, Lustgarten Foundation for Pancreatic Cancer Research, Commonwealth Fund, Burroughs Wellcome Career Award for Medical Scientists, Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Bloomberg Philanthropies, Mark Foundation for Cancer Research, NIH Cancer Center Support Grant P30 CA006973 and National Cancer Institute grant R37 CA230400. A.H.P., B.J.M., J.D. and S.R.D. were supported by NIH T32 grant GM136577. M.F.K. was supported by NIH T32 grant AR048522.
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A.H.P. wrote the original draft of the manuscript. A.H.P., M.S.H., M.F.K., E.H.-C.H., J.D., S.R.D., B.J.M., C.B., D.M.P., S.B.G., N.P., K.W.K., B.V. and S.Z. reviewed and edited the manuscript.
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The Johns Hopkins University has filed patent applications related to technologies described in this paper, on which A.H.P., M.S.H., E.H.-C.H., J.D., B.J.M., N.P., K.W.K., B.V., D.M.P. and S.Z. are listed as inventors: HLA-restricted epitopes encoded by somatically mutated genes (15/560,241, USPTO; 2016235251, European Patent Office); MANAbodies and Methods of Using (16/614,005, USPTO; 18802867.4, European Patent Office); MANAbodies Targeting Tumor Antigens and Methods of Using (63/059,638, USPTO; PCT/US2020/065617, World IP Organization). These applications include methods for identifying public neoantigens and the development of therapeutic agents that target these neoantigens. B.V., K.W.K. and N.P. are founders of Thrive Earlier Detection. K.W.K. and N.P. are consultants to Thrive Earlier Detection and were on its Board of Directors. B.V., K.W.K., N.P. and S.Z. own equity in Exact Sciences. B.V., K.W.K., N.P., S.Z. and D.M.P. are founders of, and serve or may serve as consultants to, ManaT Bio, and hold or may hold equity in ManaT Holdings, LLC. B.V., K.W.K., N.P. and S.Z. are founders of, hold equity in and serve as consultants to Personal Genome Diagnostics. S.Z. has a research agreement with BioMed Valley Discoveries. S.B.G. is a founder of and holds equity in AMS. K.W.K. and B.V. are consultants to Sysmex, Eisai and Cage Pharma and hold equity in Cage Pharma. B.V. is also a consultant to Catalio. K.W.K., B.V., S.Z. and N.P. are consultants to and hold equity in NeoPhore. N.P. is an advisor to and holds equity in Cage Pharma. C.B. is a consultant to DePuy Synthes and Bionaut Labs. The companies named above, as well as other companies, have licensed previously described technologies related to the work described in this paper from Johns Hopkins University. B.V., K.W.K., S.Z., N.P. and C.B. are inventors on some of these technologies. Licenses to these technologies are or will be associated with equity or royalty payments to the inventors, as well as to Johns Hopkins University. The terms of all of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. M.F.K. received personal fees from Bristol Myers Squibb and Celltrion. D.M.P. reports grant and patent royalties through his institution from Bristol Myers Squibb, a grant from Compugen, stock from Trieza Therapeutics and Dracen Pharmaceuticals and founder equity from Potenza; is a consultant for Aduro Biotech, Amgen, AstraZeneca (MedImmune/Amplimmune), Bayer, DNAtrix, Dynavax Technologies Corporation, Ervaxx, FLX Bio, Rock Springs Capital, Janssen, Merck, Tizona and Immunomic Therapeutics; is on the scientific advisory board of Five Prime Therapeutics, Catalio and WindMIL; and is on the board of directors for Dracen Pharmaceuticals.
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Pearlman, A.H., Hwang, M.S., Konig, M.F. et al. Targeting public neoantigens for cancer immunotherapy. Nat Cancer 2, 487–497 (2021). https://doi.org/10.1038/s43018-021-00210-y
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DOI: https://doi.org/10.1038/s43018-021-00210-y
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