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Recruitment of CD103+ dendritic cells via tumor-targeted chemokine delivery enhances efficacy of checkpoint inhibitor immunotherapy

Title: Recruitment of CD103+ dendritic cells via tumor-targeted chemokine delivery enhances efficacy of checkpoint inhibitor immunotherapy
Authors: Williford, J-M
Ishihara, J
Ishihara, A
Mansurov, A
Hosseinchi, P
Marchell, TM
Potin, L
Swartz, MA
Hubbell, JA
Item Type: Journal Article
Abstract: Although a clinical breakthrough for cancer treatment, it remains that a minority of patients respond to checkpoint inhibitor (CPI) immunotherapy. The composition of tumor-infiltrating immune cells has been identified as a key factor influencing CPI therapy success. Thus, enhancing tumor immune cell infiltration is a critical challenge. A lack of the chemokine CCL4 within the tumor microenvironment leads to the absence of CD103+ dendritic cells (DCs), a crucial cell population influencing CPI responsiveness. Here, we use a tumor stroma–targeting approach to deliver CCL4; by generating a fusion protein of CCL4 and the collagen-binding domain (CBD) of von Willebrand factor, we show that CBD fusion enhances CCL4 tumor localization. Intravenous CBD-CCL4 administration recruits CD103+ DCs and CD8+ T cells and improves the antitumor effect of CPI immunotherapy in multiple tumor models, including poor responders to CPI. Thus, CBD-CCL4 holds clinical translational potential by enhancing efficacy of CPI immunotherapy.
Issue Date: Dec-2019
Date of Acceptance: 21-Oct-2019
URI: http://hdl.handle.net/10044/1/83366
DOI: 10.1126/sciadv.aay1357
ISSN: 2375-2548
Publisher: American Association for the Advancement of Science
Start Page: 1
End Page: 15
Journal / Book Title: Science Advances
Volume: 5
Issue: 12
Copyright Statement: © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
Publication Status: Published
Online Publication Date: 2019-12-11
Appears in Collections:Bioengineering



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