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Engineering advanced cancer therapies with synthetic biology

Nature Reviews Cancer volume 19, pages 187–195 (2019)Cite this article

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Abstract

Engineered immune-cell-based cancer therapies have demonstrated robust efficacy in B cell malignancies, but challenges such as the lack of ideal targetable tumour antigens, tumour-mediated immunosuppression and severe toxicity still hinder their therapeutic efficacy and broad applicability. Synthetic biology can be used to overcome these challenges and create more robust, effective adaptive therapies that enable the specific targeting of cancer cells while sparing healthy cells. In this Progress article, we review recently developed gene circuit therapies for cancer using immune cells, nucleic acids and bacteria as chassis. We conclude by discussing outstanding challenges and future directions for realizing these gene circuit therapies in the clinic.

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Fig. 1: Synthetic biology approaches that increase chimeric antigen receptor T cell antitumour specificity.
Fig. 2: Split receptor designs to regulate T cell responses.
Fig. 3: Nucleic acid-based circuits for targeting cancer cells.

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Acknowledgements

T.K.L. is supported by the Department of Defense (W81XWH-16-1-0565 and W81XWH-18-1-0513) and the Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology Bridge Project. M.-R.W. is supported by the Department of Defense (W81XWH-16-1-0452).

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Author notes

  1. These authors contributed equally: Ming-Ru Wu, Barbara Jusiak

Authors and Affiliations

  1. Synthetic Biology Group, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA

    Ming-Ru Wu, Barbara Jusiak & Timothy K. Lu

  2. Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Timothy K. Lu

  3. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA

    Timothy K. Lu

  4. Biophysics Program, Harvard University, Boston, MA, USA

    Timothy K. Lu

  5. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA

    Timothy K. Lu

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M.-R.W. and B.J. contributed equally. All authors discussed the contents and wrote the article.

Corresponding author

Correspondence to Timothy K. Lu.

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Competing interests

M.-R.W. and T.K.L. have filed patent applications on part of work discussed in this article. T.K.L. is a co-founder of BiomX, Corvium, Eligo Biosciences, Engine Biosciences, Senti Biosciences, Synlogic and Tango Therapeutics. T.K.L. also holds financial interests in AmpliPhi, IndieBio and Nest.Bio. B.J. declares no competing interests.

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Wu, MR., Jusiak, B. & Lu, T. Engineering advanced cancer therapies with synthetic biology. Nat Rev Cancer 19, 187–195 (2019). https://doi.org/10.1038/s41568-019-0121-0

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