Cancer nanomedicine for combination cancer immunotherapy

Abstract

Cancer immunotherapy is revolutionizing oncology. However, dose-limiting toxicities and low patient response rates remain major challenges in the clinic. Cancer nanomedicine in combination with immunotherapies offers the possibility to amplify antitumour immune responses and to sensitize tumours to immunotherapies in a safe and effective manner. In this Review, we discuss opportunities for combination immunotherapy based on nanoparticle platforms designed for chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy and gene therapy. We highlight how nanoparticles can be used to reprogramme the immunosuppressive tumour microenvironment and to trigger systemic antitumour immunity, synergizing with immunotherapies against advanced cancer. Finally, we discuss strategies to improve tumour and immune cell targeting while minimizing toxicity and immune-related adverse events, and we explore the potential of theranostic nanoparticles for combination immunotherapy.

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Fig. 1: Potential clinical benefits of combination nano-immunotherapy.
Fig. 2: Nanomedicine approaches for combination cancer immunotherapy.
Fig. 3: Immune cells in the tumour microenvironment as potential targets for nano-immunotherapy.

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Acknowledgements

This work was supported in part by the US National Institutes of Health (NIH) (R01AI127070, R01EB022563, R01CA210273, R01CA223804 and U01CA210152), the Michigan Translational Research and Commercialization (MTRAC) for Life Sciences Hub, a University of Michigan (UM) Forbes Institute for Cancer Discovery Pilot Grant and the Emerald Foundation. J.J.M. is a Young Investigator supported by the Melanoma Research Alliance (348774), the US Department of Defense (DoD) Congressionally Directed Medical Research Programs (CDMRP) Peer Reviewed Cancer Research Program (W81XWH-16-1-0369) and a US National Science Foundation (NSF) CAREER Award (1553831). C.P. acknowledges financial support from the UM TEAM Training Program (DE007057 from the US National Institute of Dental and Craniofacial Research (NIDCR)). Opinions interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the DoD.

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J.N., S.S. and J.J.M. discussed content, researched data and wrote the manuscript. K.S.P. aided in the figure design and prepared the table. W.Z. and L.D.S. contributed to the revision of the manuscript. All authors reviewed and edited the manuscript.

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Correspondence to James J. Moon.

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A patent application for nanodisc technology has been filed with J.J.M. as an inventor, and J.J.M. is a co-founder of EVOQ Therapeutics, which develops nanodisc technology for cancer immunotherapy. All other authors declare no competing interests.

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Nam, J., Son, S., Park, K. et al. Cancer nanomedicine for combination cancer immunotherapy. Nat Rev Mater 4, 398–414 (2019). https://doi.org/10.1038/s41578-019-0108-1

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