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  • Review Article
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Advances in targeting cell surface signalling molecules for immune modulation

Key Points

  • Cell surface signalling molecules are important therapeutic targets for the treatment of various human diseases, including cancer and autoimmune disorders.

  • Immunomodulatory monoclonal antibodies or recombinant fusion proteins targeting signalling molecules on immune cells have become one of the most promising approaches for the treatment of human diseases.

  • With the promise to generate long-lasting tolerance in autoimmunity or memory responses against tumours, immunomodulatory biologics represent a distinctive class of drugs that target and correct aberrant immune responses.

  • Immunomodulatory monoclonal antibodies or recombinant fusion proteins that target different immunomodulatory pathways could be used in combination to maximize the effect, and are becoming an essential building block for future combination therapies with other therapeutic approaches.

Abstract

The past decade has witnessed a surge in the development of immunomodulatory approaches to combat a broad range of human diseases, including cancer, viral infections, autoimmunity and inflammation as well as in the prevention of transplant rejection. Immunomodulatory approaches mostly involve the use of monoclonal antibodies or recombinant fusion proteins that target cell surface signalling molecules on immune cells to drive immune responses towards the desired direction. Advances in our understanding of the human immune system, along with valuable lessons learned from the first generation of therapeutic biologics, are aiding the design of the next generation of immunomodulatory biologics with better therapeutic efficacy, minimized adverse effects and long-lasting clinical benefit. The recent encouraging results from antibodies targeting programmed cell death protein 1 (PD1) and B7 homolog 1 (B7H1; also known as PDL1) for the treatment of various advanced human cancers show that immunomodulatory therapy has come of age.

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Figure 1: Cell surface signalling molecules as important therapeutic targets.
Figure 2: Immune modulation of the priming and the effector phase of lymphocyte activation.
Figure 3: B7–CD28 family and newly discovered interactions.

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Acknowledgements

The authors thank B. Cadugan for manuscript editing. This work has been supported by the US National Institutes of Health (NIH) grants CA142779, CA121974, CA97085, CA16359, CA86721, CA113341 and AI72592.

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NZB/NZW F1 mouse model

The F1 generation of the cross between New Zealand black (NZB) mice and New Zealand white (NZW) mice. NZB/NZW F1 mice have a disease that closely resembles the human disease systemic lupus erythematosus.

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Yao, S., Zhu, Y. & Chen, L. Advances in targeting cell surface signalling molecules for immune modulation. Nat Rev Drug Discov 12, 130–146 (2013). https://doi.org/10.1038/nrd3877

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