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Enhancing cancer immunotherapy with nanomedicine

Abstract

Therapeutic targeting of the immune system in cancer is now a clinical reality and marked successes have been achieved, most notably through the use of checkpoint blockade antibodies and chimeric antigen receptor T cell therapy. However, efforts to develop new immunotherapy agents or combination treatments to increase the proportion of patients who benefit have met with challenges of limited efficacy and/or significant toxicity. Nanomedicines — therapeutics composed of or formulated in carrier materials typically smaller than 100 nm — were originally developed to increase the uptake of chemotherapy agents by tumours and to reduce their off-target toxicity. Here, we discuss how nanomedicine-based treatment strategies are well suited to immunotherapy on the basis of nanomaterials’ ability to direct immunomodulators to tumours and lymphoid organs, to alter the way biologics engage with target immune cells and to accumulate in myeloid cells in tumours and systemic compartments. We also discuss early efforts towards clinical translation of nanomedicine-based immunotherapy.

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Fig. 1: Nanomedicines allow unique modes of action in immunotherapy.
Fig. 2: Nanomedicines improve tumour retention and lymph node trafficking.
Fig. 3: Systemic targeting of tumours by intravenously administered nanomedicines.
Fig. 4: Enhancing cellular immunity of cancer.

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Acknowledgements

This work was supported in part by the US National Institutes of Health (awards CA235375, EB022433 and CA206218), the Mayo Clinic–Koch Institute Cancer Solutions Team Grant funding, the Marble Center for Nanomedicine and the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University. D.J.I. is an investigator of the Howard Hughes Medical Institute.

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Correspondence to Darrell J. Irvine.

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D.J.I. and E.L.D. are co-inventors on patents related to nanoparticle delivery of innate immune stimulators assigned to Massachusetts Institute of Technology (MIT). D.J.I. is an inventor on patents related to nanomedicine-based immunotherapy assigned to MIT that have been licensed to Torque Therapeutics, Elicio Therapeutics and Strand Therapeutics, of which D.J.I. is a co-founder.

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Glossary

Cyclic GMP–AMP synthase–stimulator of interferon genes pathway

(cGAS–STING pathway). An intracellular signalling pathway that responds to cytosolic double-stranded DNA through the sensor enzyme cGAS to produce the second messenger cyclic GMP–AMP, which subsequently activates STING and can stimulate cells to produce type I interferons and other cytokines.

Abscopal response

Immunological response to radiotherapy or other localized therapies whereby the treatment of a malignant lesion results in the regression or stabilization of distant, non-treated lesions.

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Irvine, D.J., Dane, E.L. Enhancing cancer immunotherapy with nanomedicine. Nat Rev Immunol 20, 321–334 (2020). https://doi.org/10.1038/s41577-019-0269-6

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