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Personalized T cell-mediated cancer immunotherapy: progress and challenges

Bethune, Michael T. and Joglekar, Alok V. (2017) Personalized T cell-mediated cancer immunotherapy: progress and challenges. Current Opinion in Biotechnology, 48 . pp. 142-152. ISSN 0958-1669 . http://resolver.caltech.edu/CaltechAUTHORS:20170509-095739381

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Abstract

Immunotherapies are yielding effective treatments for several previously untreatable cancers. Until recently, vaccines and adoptive cell therapies have been designed to target public tumor antigens common to multiple patients rather than private antigens specific to a single patient. Due to the difficulty of identifying public antigens that are expressed exclusively on tumor cells, these studies have yielded both clinical successes and serious immune-related adverse events. Multiple avenues of research now underscore the centrality of tumor-specific mutated private antigens to endogenous anti-tumor immunity. Immunotherapies that target these neoantigens may enable safer and more durable tumor regression, but personalized targeting presents a number of challenges. Foremost among these is to develop processes that accelerate advancement from neoantigen discovery to use of these neoantigens as vaccines or as targets for adoptive cell therapies. Exome sequencing has facilitated discovery of neoantigens for melanoma and other highly mutated cancers. New technologies – possibly proceeding from T cell receptor repertoire sequencing – are needed to identify antigens for cancers with low mutational burden and few neoantigens. In this review, we discuss progress toward personalizing T cell-mediated immunotherapy for cancer as well as challenges going forward.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.copbio.2017.03.024DOIArticle
http://www.sciencedirect.com/science/article/pii/S095816691630283XPublisherArticle
Additional Information:© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/). Available online 8 May 2017. We thank David Baltimore, Owen Witte, Antoni Ribas, Christopher Seet, Eric Gschweng, Jocelyn Kim, Arnav Mehta, Stephanie Wong, and Donald Kohn for their critiques of the manuscript. M.T.B. is supported by the Prostate Cancer Foundation Challenge award 15CHAL02 and the Parker Institute for Cancer Immunotherapy. A.V.J. is supported by the Caltech Innovation Initiative (CI2) award and the California Institute of Regenerative Medicine award DISC2-09123.
Funders:
Funding AgencyGrant Number
Prostate Cancer Foundation15CHAL02
Parker Institute for Cancer ImmunotherapyUNSPECIFIED
Caltech Innovation Initiative (CI2)UNSPECIFIED
California Institute for Regenerative Medicine (CIRM)DISC2-09123
Record Number:CaltechAUTHORS:20170509-095739381
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20170509-095739381
Official Citation:Michael T Bethune, Alok V Joglekar, Personalized T cell-mediated cancer immunotherapy: progress and challenges, Current Opinion in Biotechnology, Volume 48, December 2017, Pages 142-152, ISSN 0958-1669, https://doi.org/10.1016/j.copbio.2017.03.024. (http://www.sciencedirect.com/science/article/pii/S095816691630283X)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:77294
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:12 May 2017 22:30
Last Modified:12 May 2017 22:30

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