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- W2330788052 abstract "rabbit anti-human CD83 antibodies prevented GVHD in mouse and human preclinical alloHCT models. A second generation human mAb 3C12C has been evaluated as a novel therapeutic (Seldon et al, in prep) and its ability to deplete activated DC and preserve protective T cell responses was investigated. Methods: Control human IgG1 (trastazumab) and 3C12C mAb were tested in human peripheral blood mononuclear cell (PBMC) cultures and in allogeneic mixed lymphocyte cultures (alloMLC) for their ability to deplete DC. The antibody was tested in a human xenogeneic TBI and anti-NK conditioned SCID mouse model of GVHD. Survival, clinical scoring and histology were used to document the effect of 3C12C compared to the control mAb. Flow cytometry and immunohistology were used to investigate CD83 induction and the effect of 3C12C on human DC and T cell biology. Results: 3C12C but not the control mAb reduced the number of CD83+ DC in PBMC cultures. The 3C12C mAb reduced T cell proliferation in the alloMLC but did not affect Cytomegalovirus specific CD8+ T cell numbers. Human cells were identified in the liver, lung, spleen and gut of the control mAb treated PBMC transplanted mice, which developed histological GVHD d+8-13. Human DC were activated by d+2 and expressed the CMRF-44 activation marker plus CD83, CD80 and CD86. Treatment with 3C12CmAb eliminated CD83+ CMRF44+ DC early post-transplant and reduced T cell activation in terms of CD25, CD69 and CD137 and cytokine expression but maintained Treg cells. Conclusion: A potential therapeutic human anti-CD83 mAb appears to induce significant immunosuppression, associated with the depletion of CMRF-44+ activated DC, whilst preserving T cell numbers." @default.
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- W2330788052 date "2015-02-01" @default.
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- W2330788052 title "Liver Transplantation for Hepatic Graft-Versus-Host-Disease: A United Network for Organ Sharing (UNOS) Database Study" @default.
- W2330788052 doi "https://doi.org/10.1016/j.bbmt.2014.11.528" @default.
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