Considerations for designing preclinical cancer immune nanomedicine studies

Abstract

Immunotherapy is known to be clinically beneficial for cancer patients and in many cases represents the new standard of care. Because of this success, the interest in integrating nanomedicine with cancer immunotherapy to further improve clinical response and toxicity profiles has grown. However, unlike conventional systemic therapies, which are directly cytotoxic to tumour cells, cancer immunotherapy relies on the host’s immune system to generate tumouricidal effects. As such, proper design of cancer immune nanomedicine requires scrutiny of tumours’ intrinsic and extrinsic factors that may impact host antitumour immunity. Here, we highlight key parameters that differentiate cancer immunotherapy from conventional cytotoxic agents, and we discuss their implications for designing preclinical cancer immune nanomedicine studies. We emphasize that these factors, including intratumoural genomic heterogeneity, commensal diversity, sexual dimorphism and biological ageing, which were largely ignored in traditional cancer nanomedicine experiments, should be carefully considered and incorporated into cancer immune nanomedicine investigations given their critical involvement in shaping the body’s antitumour immune responses.

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Fig. 1: Increasing number of publications and total citations of cancer immune nanomedicine studies over the years.
Fig. 2: Gut microbiota influences responses and toxicities of cancer immunotherapy.
Fig. 3: Age-related changes in the immune system.
Fig. 4: Toxicity and treatment response profiles of cancer-immune and cytotoxic therapies.

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Acknowledgements

This work is supported by the Cancer Prevention and Research Institute of Texas (grant RR180017) (W.J.), the National Cancer Institute (grant K08CA241070) (W.J.), the Susan G. Komen Foundation (grant CCR19605871) (W.J.), the American Brain Tumor Association (grant DG1900021) (W.J.), the National Institute of Neurological Disorders and Stroke (grant R01 NS104315) (B.Y.S.K.) and the Department of Defense (grant W81XWH-19-1-0325) (B.Y.S.K.). The authors would like to thank Dr Damiana Chiavolini from the Department of Radiation Oncology at UT Southwestern Medical Center for editorial help with the manuscript.

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Correspondence to Wen Jiang or Betty Y. S. Kim.

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Peer review information Nature Nanotechnology thanks James Moon and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Jiang, W., Wang, Y., Wargo, J.A. et al. Considerations for designing preclinical cancer immune nanomedicine studies. Nat. Nanotechnol. 16, 6–15 (2021). https://doi.org/10.1038/s41565-020-00817-9

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