A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope.

dc.contributor.author

Swartz, Adam M

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Congdon, Kendra L

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Nair, Smita K

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Li, Qi-Jing

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Herndon, James E

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Suryadevara, Carter M

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Riccione, Katherine A

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Archer, Gary E

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Norberg, Pamela K

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Sanchez-Perez, Luis A

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Sampson, John H

dc.date.accessioned

2021-04-01T20:18:35Z

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2021-04-01T20:18:35Z

dc.date.issued

2021-01-18

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2021-04-01T20:18:33Z

dc.description.abstract

Personalized cancer vaccines targeting neoantigens arising from somatic missense mutations are currently being evaluated for the treatment of various cancers due to their potential to elicit a multivalent, tumor-specific immune response. Several cancers express a low number of neoantigens; in these cases, ensuring the immunotherapeutic potential of each neoantigen-derived epitope (neoepitope) is crucial. In this study, we discovered that therapeutic vaccines targeting immunodominant major histocompatibility complex (MHC) I-restricted neoepitopes require a conjoined helper epitope in order to induce a cytotoxic, neoepitope-specific CD8+ T-cell response. Furthermore, we show that the universally immunogenic helper epitope P30 can fulfill this requisite helper function. Remarkably, conjoined P30 was able to unveil immune and antitumor responses to subdominant MHC I-restricted neoepitopes that were, otherwise, poorly immunogenic. Together, these data provide key insights into effective neoantigen vaccine design and demonstrate a translatable strategy using a universal helper epitope that can improve therapeutic responses to MHC I-restricted neoepitopes.

dc.identifier

10.1038/s41541-020-00273-5

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2059-0105

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2059-0105

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https://hdl.handle.net/10161/22510

dc.language

eng

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Springer Science and Business Media LLC

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NPJ vaccines

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10.1038/s41541-020-00273-5

dc.title

A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope.

dc.type

Journal article

duke.contributor.orcid

Nair, Smita K|0000-0001-7019-1912

duke.contributor.orcid

Li, Qi-Jing|0000-0002-0542-9784

duke.contributor.orcid

Sampson, John H|0000-0002-0104-7658

pubs.begin-page

12

pubs.issue

1

pubs.organisational-group

School of Medicine

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Duke Cancer Institute

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Pathology

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Neurosurgery

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Surgery, Surgical Sciences

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Duke

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Institutes and Centers

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Clinical Science Departments

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Surgery

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Immunology

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Orthopaedics

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Radiation Oncology

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Basic Science Departments

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Biostatistics & Bioinformatics

pubs.publication-status

Published

pubs.volume

6

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