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  4. Recruitment of CD103(+) dendritic cells via tumor-targeted chemokine delivery enhances efficacy of checkpoint inhibitor immunotherapy
 
research article

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

Williford, John-Michael
•
Ishihara, Jun
•
Ishihara, Ako
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December 1, 2019
Science Advances

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.

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content-advances-5-12-eaay1357-full.pdf

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http://purl.org/coar/version/c_970fb48d4fbd8a85

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openaccess

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CC BY-NC

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b7169872ff7fde4167603208b7a0ca03

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