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The enhanced in vitro hematopoietic activity of leridistim, a chimeric dual G-CSF and IL-3 receptor agonist

Leukemia volume 16, pages 316–326 (2002)Cite this article

Abstract

The in vitro activity of leridistim was characterized for cell proliferation, generation of colony-forming units (CFU) and differentiation of CD34+ cells. In AML-193.1.3 cells, leridistim exhibited a significant increase in potency compared to rhG-CSF, SC-65303 (an IL-3 receptor agonist) or an equimolar combination of rhG-CSF and SC-65303. CFU-GM assays demonstrated that at 50% of the maximum response, the relative potency of leridistim was 12-fold greater than the combination of rhG-CSF and rhIL-3 and 44-fold more potent than rhG-CSF alone. In multi-lineage CFU assays, a combination of erythropoietin (rhEPO) and leridistim resulted in greater numbers of BFU-E, CFU-GEMM and CFU-Mk than rhEPO alone. Ex vivo culture of peripheral blood or bone marrow CD34+ cells with leridistim substantially increased total viable cells over cultures stimulated with rhG-CSF, SC-65303, or a combination of rhG-CSF and SC-65303. Culture with leridistim, resulted in a greater increase in myeloid (CD15+/CD11b+), monocytic (CD41−/CD14+) and megakaryocytic (CD41+/CD14−) precursor cells without depleting the progenitor pool (CD34+/CD15−/CD11b−). These results demonstrate that leridistim is a more potent stimulator of hematopoietic proliferation and differentiation than the single receptor agonists (rhG-CSF and SC-65303) either alone or combined. These unique attributes suggest that leridistim may enhance hematopoietic reconstitution following myelosuppressive chemotherapy.

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Acknowledgements

We gratefully acknowledge Kathryn Young for her technical assistance, Alfred Balch and Jeanne Sebaugh for statistical analysis, and Charles McWherter for critical reading of the manuscript.

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  1. AL Abegg and LE Vickery: The first two authors contributed equally

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  1. Pharmacia Discovery Research, 700 Chesterfield Village Parkway North, St Louis, MO 63198, USA

    AL Abegg, LE Vickery, ME Bremer, AM Donnelly, PD Doshi, ML Evans, TL Thurman, SR Braford, MH Caparon, SC Bauer, JG Giri, JK Welply, JP McKearn & WG Smith

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Abegg, A., Vickery, L., Bremer, M. et al. The enhanced in vitro hematopoietic activity of leridistim, a chimeric dual G-CSF and IL-3 receptor agonist. Leukemia 16, 316–326 (2002). https://doi.org/10.1038/sj.leu.2402366

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