Engineering patient-specific cancer immunotherapies

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Abstract

Research into the immunological processes implicated in cancer has yielded a basis for the range of immunotherapies that are now considered the fourth pillar of cancer treatment (alongside surgery, radiotherapy and chemotherapy). For some aggressive cancers, such as advanced non-small-cell lung carcinoma, combination immunotherapies have resulted in unprecedented treatment efficacy for responding patients, and have become frontline therapies. Individualized immunotherapy, enabled by the identification of patient-specific mutations, neoantigens and biomarkers, and facilitated by advances in genomics and proteomics, promises to broaden the responder patient population. In this Perspective, we give an overview of immunotherapies leveraging engineering approaches, including the design of biomaterials, delivery strategies and nanotechnology solutions, for the realization of individualized cancer treatments such as nanoparticle vaccines customized with neoantigens, cell therapies based on patient-derived dendritic cells and T cells, and combinations of theranostic strategies. Developments in precision cancer immunotherapy will increasingly rely on the adoption of engineering principles.

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Fig. 1: Engineering approaches for personalized immunotherapy.
Fig. 2: Preparation process for a personalized vaccine.
Fig. 3: Personalized neoantigen vaccination with sHDL nanodiscs.
Fig. 4: ‘Albumin-hitchhiking’ strategy for neoantigen vaccination.
Fig. 5: Targeted delivery of CAR genes to peripheral T lymphocytes in situ.
Fig. 6: Combination of chemotherapy and photothermal therapy for the elimination of distant secondary tumours.
Fig. 7: Systemic immune responses via radiation therapy combined with radiodynamic therapy.

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Acknowledgements

This work was supported in part by NIH (grant no. R01EB022563, R01CA210273, R01CA223804, R01AI127070, R21NS091555, R01HL134569, U01CA210152, R37NS094804, RO1NS105556, R21NS107894, RO1NS096756, UO1CA224160), MTRAC for Life Sciences Hub, UM Forbes Institute for Cancer Discovery Pilot Grant and Emerald Foundation. J.J.M. is a Young Investigator supported by the Melanoma Research Alliance (grant no. 348774), DoD/CDMRP Peer Reviewed Cancer Research Program (grant no. W81XWH-16-1-0369), and NSF CAREER Award (grant no. 1553831). L.S. acknowledges financial support from the UM Pharmacological Sciences Training Program (PSTP) (grant no. GM007767 from NIGMS). K.S.P. acknowledges financial support from the UM TEAM Training Program (grant no. DE007057 from NIDCR). Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defence.

Author information

L.S., K.S.P, and J.J.M. discussed content, researched data and wrote the manuscript. Q.L., P.R.L, M.G.C. and A.S. contributed to the discussion.

Correspondence to James J. Moon.

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Competing interests

A patent application for the nanodisc vaccines has been filed, with J.J.M. and A.S. as inventors, and J.J.M. and A.S. as co-founders of EVOQ Therapeutics, LLC., which develops the technology.

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Scheetz, L., Park, K.S., Li, Q. et al. Engineering patient-specific cancer immunotherapies. Nat Biomed Eng 3, 768–782 (2019) doi:10.1038/s41551-019-0436-x

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