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Immunotherapy

Cancer cells BiTE the dust

Nature Reviews Drug Discovery volume 7, page 804 (2008)Cite this article

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The antibody construct blinatumomab, designed as a bispecific T-cell engager (BiTE), was based on single-chain antibodies with dual specificity for CD19 (B cells) and CD3, the T-cell receptor complex. Previous in vitro studies had demonstrated that, in the presence of CD19-expressing target cells, it can induce the polyclonal activation of peripheral human T cells and target cell lysis. Importantly, the activation of T cells was strictly dependent on the presence of the target cells — a major safety concern, as polyclonal activation can lead to a potentially fatal cytokine-release syndrome (cytokine storm).

In a Phase I clinical trial, blinatumomab was tested in 38 patients with relapsed B-cell non-Hodgkin's lymphoma. The majority of the patients had already undergone multiple rounds of chemotherapy and treatment with rituximab, a B-cell-depleting antibody. Blinatumomab was administered by continuous intravenous infusion with a portable minipump system over a period of 4–8 weeks. Doses as low as 0.005 mg per m2 were shown to lead to an elimination of target cells in the blood, and all seven patients in the treatment group with the highest dose of 0.06 mg per m2 experienced tumour regression. Four patients achieved a complete response (disappearance of all known lesions and clearance of bone marrow from lymphoma cells). Moreover, no relapses have been observed so far in responding patients treated with doses of 0.03 mg per m2 or higher.

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References

ORIGINAL RESEARCH PAPER

  1. Bargou, R. et al. Tumor regression in cancer patients by very low doses of a T cell engaging antibody. Science 321, 974–977 (2008)

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FURTHER READING

  1. Brischwein, K. et al. Strictly target cell-dependent activation of T cells by bispecific single-chain antibody constructs of the BiTE class. J. Immunother. 30, 798–807 (2007)

    Article  CAS  Google Scholar 

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Authors
  1. Alexandra Flemming
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Flemming, A. Cancer cells BiTE the dust. Nat Rev Drug Discov 7, 804 (2008). https://doi.org/10.1038/nrd2690

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  • DOI: https://doi.org/10.1038/nrd2690

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