Anti-class II -DR humanized monoclonal antibody, IMMU-114, blocks allogeneic immune response.

BACKGROUND: The effect of a humanized anti-human leukocyte antigen-DR monoclonal antibody, IMMU-114, on the allogeneic immune response was investigated in vitro. METHODS: Responder peripheral blood mononuclear cells were cocultured with inactivated self or allogeneic stimulator peripheral blood mononuclear cells in the presence of control antibody or IMMU-114. Thymidine incorporation rates were then measured. Phenotypic changes in peripheral blood mononuclear cells and the intracellular Th1-type cytokines interleukin-2, interferon-gamma, and tumor necrosis factor-alpha were analyzed using flow cytometry. The concentrations of interleukin-2, interferon-gamma, and tumor necrosis factor-alpha in the mixed lymphocyte reaction culture medium were measured. RESULTS: Thymidine incorporation rates at a 1:1 responder/stimulator ratio of allogeneic, allogeneic + IMMU-114, self, and self + IMMU-114 were 22,080.7 +/- 602.4, 2,254.5 +/- 118.1, 1,284.0 +/- 227.8, and 494.5 +/- 27.5 cpm, respectively (P = .038). IMMU-114 decreased the frequencies of human leukocyte antigen-DR-expressing CD16+56+ NK cells, CD19+ B cells, and CD3+25+ activated T cells. CONCLUSION: Intracellular cytokine assay and measurement of Th1-type cytokines in the mixed lymphocyte reaction culture medium revealed that IMMU-114 significantly decreased the titers of interleukin-2, interferon-gamma, and tumor necrosis factor-alpha. IMMU-114 significantly suppresses the allogeneic immune response in vitro, partly through inhibition of the Th1 response. (C) 2012 Elsevier Inc. All rights reserved.