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IMMUNOTHERAPY

Checkpoint inhibition in the bone marrow

Nature Biomedical Engineering volume 2, pages 793–794 (2018)Cite this article

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The coupling of blood platelets bearing anti-programmed cell death protein 1 antibodies to haematopoietic stem cells enables delivery of checkpoint-blockade therapy to bone marrow to promote T-cell-mediated control of leukaemia in mice.

Acute myeloid leukaemia (AML) is a malignancy of clonally expanding myeloid progenitor cells in the bone marrow and blood. The mainstay treatment of AML, based mainly on chemotherapeutic drugs with or without haematopoietic stem cell (HSC) transplantation, has remained largely unchanged over several decades and often fails in patients, making AML the leading cause of leukaemia-related deaths in Western countries. The success of immunotherapies for melanoma and other solid tumours owing to the development of immune checkpoint inhibitors (such as antibodies to programmed cell death protein 1 (PD-1)) — a breakthrough in cancer therapeutics, as acknowledged by the 2018 Nobel Prize in Medicine — has prompted the application of checkpoint inhibitors to AML and other haematological malignancies. Encouraging data from preclinical models suggest a therapeutic role for immune checkpoint blockade in AML1, but the first clinical trials using checkpoint inhibitors as single-agent therapy in this disease have shown only modest clinical efficacy, and it seems unlikely that any of these compounds, when used as monotherapy, will cure the disease2. Therefore, these therapeutic modalities require optimization to improve clinical efficacy, and potential combination strategies that rely on the mechanistic understanding of tumour immune control and escape mechanisms should be explored. Reporting in Nature Biomedical Engineering, Zhen Gu and colleagues now show effective control of the expansion of AML cells in mice following treatment with engineered cell constructs consisting of HSCs (S), platelets (P) and anti-PD-1 antibodies (aPD-1)3. The S–P–aPD-1 construct enables targeted delivery of the immune checkpoint inhibitor aPD-1 into the bone marrow3, effectively targeting the main site of leukaemia clonal expansion.

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Fig. 1: Re-activation of AML-targeting T cells via delivery of aPD-1 to the bone marrow of leukaemic mice by means of a platelet–HSC construct.

References

  1. Zhang, L., Gajewski, T. F. & Kline, J. Blood 114, 1545–1552 (2009).

    CAS  Article  Google Scholar 

  2. Boddu, P. et al. Leuk. Lymphoma 59, 790–802 (2018).

    CAS  Article  Google Scholar 

  3. Hu, Q. et al. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-018-0310-2 (2018).

  4. Vidriales, M. B. et al. Ann. Hematol. 67, 217–222 (1993).

    CAS  Article  Google Scholar 

  5. Van den Hove, L. E. et al. Leuk. Res. 22, 175–184 (1998).

    Article  Google Scholar 

  6. Yang, H. et al. Leukemia 28, 1280–1288 (2014).

    CAS  Article  Google Scholar 

  7. Coles, S. J. et al. Leukemia 29, 1952–1954 (2015).

    CAS  Article  Google Scholar 

  8. Alexandrov, L. B. et al. Nature 500, 415–421 (2013).

    CAS  Article  Google Scholar 

  9. Roh, W. et al. Sci. Transl. Med. 9, eaah3560 (2017).

    Article  Google Scholar 

  10. Li, S. et al. Nat. Med. 22, 792–799 (2016).

    CAS  Article  Google Scholar 

  11. Geiger, T. L. & Rubnitz, J. E. Discov. Med. 19, 275–284 (2015).

    PubMed  PubMed Central  Google Scholar 

  12. Daver, N. et al. Leukemia 32, 1094–1105 (2018).

    CAS  Article  Google Scholar 

  13. Klinger, M., Benjamin, J., Kischel, R., Stienen, S. & Zugmaier, G. Immunol. Rev. 270, 193–208 (2016).

    CAS  Article  Google Scholar 

Download references

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  1. Molecular Genetics, German Cancer Research Center, Heidelberg, Germany

    Martina Seiffert

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  1. Martina Seiffert
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Correspondence to Martina Seiffert.

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Seiffert, M. Checkpoint inhibition in the bone marrow. Nat Biomed Eng 2, 793–794 (2018). https://doi.org/10.1038/s41551-018-0319-6

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