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Cancer Immunology Research
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Cancer Immunology at the Crossroads

Personal Neoantigen Cancer Vaccines: A Road Not Fully Paved

Edward F. Fritsch, Ute E. Burkhardt, Nir Hacohen and Catherine J. Wu
Edward F. Fritsch
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
2Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
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Ute E. Burkhardt
3Accelerating Cancer Immunotherapy Research, Cambridge, Massachusetts.
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  • ORCID record for Ute E. Burkhardt
Nir Hacohen
2Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
4Department of Medicine, Harvard Medical School, Boston, Massachusetts.
5Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts.
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Catherine J. Wu
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
2Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
4Department of Medicine, Harvard Medical School, Boston, Massachusetts.
6Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
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  • For correspondence: cwu@partners.org
DOI: 10.1158/2326-6066.CIR-20-0526 Published December 2020
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Abstract

Personal neoantigen–based cancer vaccines are designed to target antigens arising from tumor-specific mutations within individual cancers and present a tremendous opportunity to capitalize on their favorable and intrinsic properties of escape from central tolerance and exquisite tumor specificity. With the endpoint of creating an optimal T-cell army to attack a tumor, neoantigen-based vaccines have demonstrated the ability to coax naïve T-cell recruits against epitopes that do not induce spontaneous immunity to raise long-lasting T-cell responses against multiple tumor-specific epitopes and subsequently to extend the breadth of responses, as immunity begets immunity via epitope spreading. Importantly, on both preclinical and clinical fronts, the association of T-cell responses to neoantigens and favorable outcomes has been demonstrated time and time again. We recognize, however, that the path forward remains long and winding and requires the field to address several key challenges, particularly overcoming evolved tumor escape mechanisms and optimizing vaccine-induced immunity. Some challenges stem from gaps in science that enable in silico prediction of antigen presentation and recognition by T-cell receptors, whereas others stem from the logistical obstacles and cost of personalization. Nevertheless, with perseverance and innovative solutions, we have little doubt that the ability of neoantigen vaccination to induce potent cancer-specific T cells will fundamentally succeed in enabling greater effectiveness of a broad array of immunotherapies. We provide our perspective on the progress and the remaining challenges to realizing the opportunity of personal neoantigen cancer vaccines.

Footnotes

  • Cancer Immunol Res 2020;8:1465–9

  • ©2020 American Association for Cancer Research.
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Cancer Immunology Research: 8 (12)
December 2020
Volume 8, Issue 12
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Personal Neoantigen Cancer Vaccines: A Road Not Fully Paved
Edward F. Fritsch, Ute E. Burkhardt, Nir Hacohen and Catherine J. Wu
Cancer Immunol Res December 1 2020 (8) (12) 1465-1469; DOI: 10.1158/2326-6066.CIR-20-0526

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Personal Neoantigen Cancer Vaccines: A Road Not Fully Paved
Edward F. Fritsch, Ute E. Burkhardt, Nir Hacohen and Catherine J. Wu
Cancer Immunol Res December 1 2020 (8) (12) 1465-1469; DOI: 10.1158/2326-6066.CIR-20-0526
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  • Article
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    • The Concept of Immunotherapy with Personalized Neoantigen Vaccines
    • Testing the Concept
    • Should We Still Be Encouraged? Challenges and Opportunities
    • A Major Speed Bump Ahead
    • Outlook
    • Disclosure of Potential Conflicts of Interest
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Cancer Immunology Research
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