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TUMOUR IMMUNOLOGY

Stop the shedding

Nature Reviews Cancer volume 18, pages 338–339 (2018)Cite this article

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As many different proteases cleave MICA and MICB, protease inhibition is not a viable option for inhibiting shedding. Therefore, Ferrari de Andrade et al. created monoclonal antibodies (mAbs) directed against the α3 domain of MICA, which is crucial for shedding. They identified three mAbs that prevented shedding of both MICA and MICB on a panel of human tumour cell lines but did not interfere with binding of MICA and MICB to NK group 2D (NKG2D) receptors, which are important for NK cell-mediated cytotoxicity. The 7C6 mAb most effectively stabilized MICA and MICB while still enabling NK cell-mediated killing of tumour cells in co-culture, so this mAb was selected for further study.

Mice do not express MICA or MICB, but human MICA is recognized by mouse NKG2D, so the therapeutic efficacy of 7C6 could be tested in syngeneic, immunocompetent mouse models of metastasis. Mouse melanoma (B16F10) or colon cancer (CT26) cell lines expressing human MICA were injected intravenously into mice, followed by injection of the 7C6 mAb starting at day 1. Colonization of the lungs was significantly reduced by 7C6 compared with a control antibody. 7C6 was also effective at blocking growth of subcutaneous MICA-expressing B16F10 cells and at reducing growth of established metastases.

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References

Original Article

  • Ferrari de Andrade, L. et al. Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science 359, 1537–1542 (2018)

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  1. Nature Reviews Cancer http://www.nature.com/nrc/

    Sarah Seton-Rogers

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  1. Sarah Seton-Rogers
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Correspondence to Sarah Seton-Rogers.

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Seton-Rogers, S. Stop the shedding. Nat Rev Cancer 18, 338–339 (2018). https://doi.org/10.1038/s41568-018-0012-9

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