Immunostimulatory nanomedicines synergize with checkpoint blockade immunotherapy to eradicate colorectal tumors

Xiaopin Duan, Christina Chan, Wenbo Han, Nining Guo, Ralph R. Weichselbaum and Wenbin Lin ()
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Xiaopin Duan: The University of Chicago
Christina Chan: The University of Chicago
Wenbo Han: The University of Chicago
Nining Guo: The University of Chicago
Ralph R. Weichselbaum: The University of Chicago
Wenbin Lin: The University of Chicago

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Nanoparticles can potentially stimulate tumour microenvironments to elicit antitumour immunity. Herein, we demonstrate effective immunotherapy of colorectal cancer via systemic delivery of an immunostimulatory chemotherapeutic combination in nanoscale coordination polymer (NCP) core-shell particles. Oxaliplatin and dihydroartemesinin have contrasting physicochemical properties but strong synergy in reactive oxygen species (ROS) generation and anticancer activity. The combined ROS generation is harnessed for immune activation to synergize with an anti-PD-L1 antibody for the treatment of murine colorectal cancer tumours. The favourable biodistribution and tumour uptake of NCPs and the absence of peripheral neuropathy allow for repeated dosing to afford 100% tumour eradication. The involvement of innate and adaptive immune systems elicit strong and long lasting antitumour immunity which prevents tumour formation when cured mice are challenged with cancer cells. The intrinsically biodegradable, well tolerated, and systemically available immunostimulatory NCP promises to enter clinical testing as an immunotherapy against colorectal cancer.

Date: 2019
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DOI: 10.1038/s41467-019-09221-x

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