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Graft-versus-host Disease

The humanized anti-HLA-DR moAb, IMMU-114, depletes APCs and reduces alloreactive T cells: implications for preventing GVHD

Bone Marrow Transplantation volume 47, pages 967–980 (2012)Cite this article

Abstract

In contrast to the conventional immunosuppressive agents and nonselective T-cell-depleting antibodies, selective depletion of donor alloreactive T cells and/or host APCs, particularly DCs, represents a novel approach that can effectively control GVHD with less or no impairment of T-cell-mediated antiviral and GVL immunity. Here we report that IMMU-114, a humanized anti-human leukocyte antigen-DR (HLA-DR) moAb, efficiently depleted human PBMCs of all APCs, including B cells, monocytes, myeloid DC type-1 (mDC1), mDC2 and plasmacytoid DCs (pDCs). Early and late apoptosis of mDC1, mDC2 and pDCs, and late apoptosis of all APC subsets, were increased by IMMU-114 treatment. Although IMMU-114 had little, if any, effect on the survival and apoptosis of non-B lymphocytes (>80% of which are T cells and ∼1-2% of T cells express HLA-DR), it selectively inhibited the proliferation of purified HLA-DR+ T cells rather than HLA-DR− T cells. As a consequence, IMMU-114 treatment resulted in suppressed T-cell proliferation and reduced CD25+ alloreactive T cells in allogeneic MLRs. Given the critical roles of APCs and alloreactive T cells in the pathogenesis of GVHD, these results suggest that IMMU-114 may have therapeutic potential against GVHD.

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Acknowledgements

This work was supported in part by NIH Grant PO1-CA103985 from the National Cancer Institute (DMG), Grant 09-1976-CCR-EO from the New Jersey Commission on Cancer Research (DMG), a grant from the MGN Foundation (XC) and a grant from the Carvel Foundation (RS).

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  1. Garden State Cancer Center, Center for Molecular Medicine and Immunology, Morris Plains, NJ, USA

    X Chen, R Stein & D M Goldenberg

  2. Immunomedics Inc., Morris Plains, NJ, USA

    C-H Chang

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Correspondence to X Chen or D M Goldenberg.

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C-HC and DMG have employment, stock and/or stock options with Immunomedics Inc., which is developing IMMU-114 and APC-targeting antibodies. The remaining authors declare no competing financial interests.

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Chen, X., Chang, CH., Stein, R. et al. The humanized anti-HLA-DR moAb, IMMU-114, depletes APCs and reduces alloreactive T cells: implications for preventing GVHD. Bone Marrow Transplant 47, 967–980 (2012). https://doi.org/10.1038/bmt.2011.203

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