Immunogenic Cell Death Amplified by Co-localized Adjuvant Delivery for Cancer Immunotherapy
Name
Immunogenic Cell Death Amplified by Co-localized Adjuvant Delivery for Cancer Immunotherapy.pdf
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1.6 MB
Format
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Checksum (MD5)
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Author(s)
Fan, Yuchen
Kuai, Rui
Xu, Yao
Ochyl, Lukasz J.
Moon, James J.
Irvine, Darrell J
Date Issued
December 2017
Journal
Nano Letters
Publisher
American Chemical Society (ACS)
Citation
Fan, Yuchen et al. “Immunogenic Cell Death Amplified by Co-Localized Adjuvant Delivery for Cancer Immunotherapy.” Nano Letters 17, 12 (November 22, 2017): 7387–7393 © 2017 American Chemical Society
Version
Author's final manuscript
Abstract
Despite their potential, conventional whole-cell cancer vaccines prepared by freeze-thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have indicated that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate antitumor immune responses. However, it remains unclear how to exploit ICD for cancer immunotherapy. Here, we present a new material-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their therapeutic potential in murine models of melanoma and colon carcinoma. We have generated immunogenically dying tumor cells surface-modified with adjuvant-loaded nanoparticles. Dying tumor cells laden with adjuvant nanodepots efficiently promote activation and antigen cross-presentation by dendritic cells in vitro and elicit robust antigen-specific CD8α+ T-cells in vivo. Furthermore, whole tumor-cell vaccination combined with immune checkpoint blockade leads to complete tumor regression in 78% of CT26 tumor-bearing mice and establishes long-term immunity against tumor recurrence. Our strategy presented here may open new doors to "personalized" cancer immunotherapy tailored to individual patient's tumor cells. Keywords: cancer immunotherapy; cancer vaccine; Cell engineering; innunogenic cell death; nanoparticle
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/ACS.NANOLETT.7B03218
