A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope.
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.
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https://hdl.handle.net/10161/22510Published Version (Please cite this version)
10.1038/s41541-020-00273-5Publication Info
(2021). A conjoined universal helper epitope can unveil antitumor effects of a neoantigen
vaccine targeting an MHC class I-restricted neoepitope. NPJ vaccines, 6(1). pp. 12. 10.1038/s41541-020-00273-5. Retrieved from https://hdl.handle.net/10161/22510.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Gerald Edward Archer
Assistant Professor of Neurosurgery
My current research focus involves the delivery of therapeutic agents for the treatment
of central nervous system neoplasia. Utilizing athymic rat models of central nervous
system neoplasia I am investigating compartmental approaches to increase therapeutic
efficacy of chemotherapeutic agents and immunoconjugates. Preclinical testing in
athymic rats of intrathecal administration of melphalan and 4-hydroperoxycyclophosphamide
have resulted in the FDA granting investigational new drug prot
James Emmett Herndon II
Professor of Biostatistics & Bioinformatics
Current research interests have application to the design and analysis of cancer clinical
trials. Specifically, interests include the use of time-dependent covariables within
survival models, the design of phase II cancer clinical trials which minimize some
of the logistical problems associated with their conduct, and the analysis of longitudinal
studies with informative censoring (in particular, quality of life studies of patients
with advanced cancer).
Qi-Jing Li
Associate Professor of Immunology
Recent clinical success in cancer immunotherapy, including immune checkpoint blockades
and chimeric antigen receptor T cells, have settled a long-debated question in the
field: whether tumors can be recognized and eliminated by our own immune system, specifically,
the T lymphocyte. Meanwhile, current limitations of these advanced treatments pinpoint
fundamental knowledge deficits in basic T cell biology, especially in the context
of tumor-carrying patients. Aiming to develop new immunotherapi
Smita K Nair
Professor in Surgery
I have 22 years of experience in the field of cancer vaccines and immunotherapy and
I am an accomplished T cell immunologist. Laboratory website:https://surgery.duke.edu/immunology-inflammation-immunotherapy-laboratory
Current projects in the Nair Laboratory:1] Dendritic cell vaccines using tumor-antigen
encoding RNA (mRNA, total tumor RNA, amplified tumor mRNA)<br
John Howard Sampson
Robert H., M.D. and Gloria Wilkins Professor of Neurosurgery, in the School of Medicine
Current research activities involve the immunotherapeutic targeting of a tumor-specific
mutation in the epidermal growth factor receptor. Approaches used to target this tumor-specific
epitope include unarmed and radiolabeled antibody therapy and cell mediated approaches
using peptide vaccines and dendritic cells. Another area of interest involves drug
delivery to brain tumors. Translational and clinical work is carried out in this area
to formulate the relationship between various direct intratu
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