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

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 (480% of which are T cells and B1-2% 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. Bone Marrow Transplantation (2012) 47, 967-980; doi: 10.1038/bmt.2011.203; published online 24 October 2011