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IMMUNOTHERAPY

Programmable bacteria as cancer therapy

Nature Medicine volume 25, pages 1030–1031 (2019)Cite this article

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Quorum-sensing bacteria can deliver a nanobody targeting the ‘don’t eat me’ ligand CD47 to tumors that results in systemic anti-tumor immunity-induced regression in mice.

The first injection of heat-killed mixtures of bacteria into patients with cancer was performed in the 1880s by William Coley, who observed anecdotal regression of solid tumors1. Although Coley’s toxins fell out of medical practice, introducing bacteria into tumors to generate an immune response remains a powerful idea. Bacteria provide adjuvants—substances such as the cell-wall components lipopolysaccharide and peptidoglycan—that activate innate immune receptors recognizing common molecular patterns found in microbes. Simple in approach and execution, intratumoral delivery of adjuvant creates an in situ vaccine. Antigens released from dying tumor cells are taken up by activated dendritic cells; these cells then migrate to draining lymph nodes and prime adaptive immunity in the form of cytotoxic T cells that seek out and destroy tumor cells. In this issue of Nature Medicine, Chowdhury et al.2 report a strategy using quorum-sensing bacteria that allows the delivery of a nanobody—a single-chain antibody fragment—that targets the phagocyte inhibitory ligand CD47 (CD47nb). This strategy was found to lead to systemic anti-tumor immunity that induced the regression of both injected and non-injected lesions in mice.

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Fig. 1: Inducing systemic anti-tumor immunity with quorum-sensing bacteria carrying nanobodies.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Michael Dougan

  2. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Michael Dougan

  3. Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA

    Stephanie K. Dougan

  4. Department of Immunology, Harvard Medical School, Boston, MA, USA

    Stephanie K. Dougan

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  1. Michael Dougan
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  2. Stephanie K. Dougan
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Correspondence to Stephanie K. Dougan.

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Dougan, M., Dougan, S.K. Programmable bacteria as cancer therapy. Nat Med 25, 1030–1031 (2019). https://doi.org/10.1038/s41591-019-0513-4

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