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Nanomaterials for T-cell cancer immunotherapy

Abstract

T-cell-based immunotherapies hold promise for the treatment of many types of cancer, with three approved products for B-cell malignancies and a large pipeline of treatments in clinical trials. However, there are several challenges to their broad implementation. These include insufficient expansion of adoptively transferred T cells, inefficient trafficking of T cells into solid tumours, decreased T-cell activity due to a hostile tumour microenvironment and the loss of target antigen expression. Together, these factors restrict the number of therapeutically active T cells engaging with tumours. Nanomaterials are uniquely suited to overcome these challenges, as they can be rationally designed to enhance T-cell expansion, navigate complex physical barriers and modulate tumour microenvironments. Here, we present an overview of nanomaterials that have been used to overcome clinical barriers to T-cell-based immunotherapies and provide our outlook of this emerging field at the interface of cancer immunotherapy and nanomaterial design.

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Fig. 1: Classes of T cells deployed in ACT.
Fig. 2: The current nanomaterial toolbox can be applied to in vivo T-cell therapies.
Fig. 3: Nanomaterials for in vivo T-cell expansion.
Fig. 4: Nanomaterials overcome physical barriers and immune-suppressive environments for T-cell therapy.
Fig. 5: NBiTEs for cancer immunotherapy.

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Acknowledgements

M.J.M. acknowledges support from a Burroughs Wellcome Fund Career Award at the Scientific Interface (CASI), a US National Institutes of Health (NIH) Director’s New Innovator Award (DP2 TR002776), a grant from the American Cancer Society (129784-IRG-16-188-38-IRG), the National Institutes of Health (NCI R01 CA241661, NCI R37 CA244911 and NIDDK R01 DK123049), an Abramson Cancer Center (ACC)–School of Engineering and Applied Sciences (SEAS) Discovery Grant (P30 CA016520), and a 2018 AACR-Bayer Innovation and Discovery Grant, Grant Number 18-80-44-MITC. M.M.B. was supported by a Tau Beta Pi Graduate Research Fellowship and an NIH Training in HIV Pathogenesis T32 Program (T32 AI007632).

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Correspondence to Michael J. Mitchell.

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C.H.J. works under a research collaboration involving the University of Pennsylvania and the Novartis Institutes of Biomedical Research, Inc. C.H.J. is an inventor of intellectual property licensed by the University of Pennsylvania to Novartis. C.H.J. has sponsored research and equity from Tmunity Therapeutics. C.H.J. is a consultant for Immune Design, Viracta and Carisma. N.C.S. holds shares in Tmunity Therapeutics and Fate Therapeutics.

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Gong, N., Sheppard, N.C., Billingsley, M.M. et al. Nanomaterials for T-cell cancer immunotherapy. Nat. Nanotechnol. 16, 25–36 (2021). https://doi.org/10.1038/s41565-020-00822-y

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