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BL22: A Milestone in Targeting CD22

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Book cover Next Generation Antibody Drug Conjugates (ADCs) and Immunotoxins

Part of the book series: Milestones in Drug Therapy ((MDT))

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Abstract

BL22 is a recombinant immunotoxin, a chimeric protein composed of an Fv fragment of the monoclonal antibody (MAb) RFB4, and a truncated portion of Pseudomonas exotoxin. The antibody fragment that binds to the target cell is internalized along with the toxin, and the toxin fragment is transported to the cytosol where it catalytically kills the cell. Preclinical development showed significant cytotoxicity and antitumor activity toward CD22+ leukemia and lymphoma cells. Phases 1 and 2 testing showed high response rates in relapsed and refractory hairy cell leukemia (HCL), with complete remission rates of 47–61% depending on the design of the trial. We did not encounter chemotherapy-type toxicities, which is understandable due to its mechanism of action. However, we did observe a completely reversible hemolytic uremic syndrome (HUS) which did not require plasmapheresis for complete resolution. BL22 has since undergone further engineering to increase binding affinity to CD22. The improved molecule, moxetumomab pasudotox, is currently undergoing pivotal phase 3 testing in HCL. BL22 was thus a mile stone in surface-targeted therapy producing a promising new treatment option for CD22+ chemotherapy-relapsed leukemia.

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Acknowledgments

This study was supported in part by the Intramural Research Program, NCI, and MedImmune.

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Authors and Affiliations

  1. Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 37/5124b, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    Robert J. Kreitman, David J. P. FitzGerald & Ira Pastan

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  1. Robert J. Kreitman
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  2. David J. P. FitzGerald
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  3. Ira Pastan
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Correspondence to Robert J. Kreitman .

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  1. NBE-Therapeutics Ltd., Basel, Switzerland

    Ulf Grawunder

  2. Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

    Stefan Barth

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Kreitman, R.J., FitzGerald, D.J.P., Pastan, I. (2017). BL22: A Milestone in Targeting CD22. In: Grawunder, U., Barth, S. (eds) Next Generation Antibody Drug Conjugates (ADCs) and Immunotoxins. Milestones in Drug Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-46877-8_8

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