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Overcoming biological barriers to improve solid tumor immunotherapy

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Abstract

Cancer immunotherapy has been at the forefront of therapeutic interventions for many different tumor types over the last decade. While the discovery of immunotherapeutics continues to occur at an accelerated rate, their translation is often hindered by a lack of strategies to deliver them specifically into solid tumors. Accordingly, significant scientific efforts have been dedicated to understanding the underlying mechanisms that govern their delivery into tumors and the subsequent immune modulation. In this review, we aim to summarize the efforts focused on overcoming tumor-associated biological barriers and enhancing the potency of immunotherapy. We summarize the current understanding of biological barriers that limit the entry of intravascularly administered immunotherapies into the tumors, in vitro techniques developed to investigate the underlying transport processes, and delivery strategies developed to overcome the barriers. Overall, we aim to provide the reader with a framework that guides the rational development of technologies for improved solid tumor immunotherapy.

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Acknowledgements

Authors acknowledge the use of Biorender.com for making graphical abstract and schematics.

Funding

This work was funded by support from National Institutes of Health (1R01HL143806-01).

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Author notes

  1. Anvay Ukidve, Katharina Cu and Ninad Kumbhojkar equally contributed to this work.

Authors and Affiliations

  1. John A Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA

    Anvay Ukidve, Katharina Cu, Ninad Kumbhojkar & Samir Mitragotri

  2. Wyss Institute of Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA

    Anvay Ukidve, Katharina Cu, Ninad Kumbhojkar & Samir Mitragotri

  3. Department of Chemical Engineering, Department of Material Science & Engineering, Department of Macromolecular Science & Engineering, Department of Biomedical Engineering, and Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA

    Joerg Lahann

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  1. Anvay Ukidve
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  2. Katharina Cu
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Contributions

AU, KC, and NK contributed equally. AU, KC, NK, JL, and SM wrote the manuscript.

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Correspondence to Samir Mitragotri.

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SM and AU are inventors on patent applications in the field of tumor immunotherapy (owned and managed by Harvard University).

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Ukidve, A., Cu, K., Kumbhojkar, N. et al. Overcoming biological barriers to improve solid tumor immunotherapy. Drug Deliv. and Transl. Res. 11, 2276–2301 (2021). https://doi.org/10.1007/s13346-021-00923-8

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