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-γ, and tumor necrosis factor-α were analyzed using flow cytometry. The concentrations of interleukin-2, interferon-γ, and tumor necrosis factor-α 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.


CONCLUSIONS
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-γ, and tumor necrosis factor-α. IMMU-114 significantly suppresses the allogeneic immune response in vitro, partly through inhibition of the Th1 response.
Dokkyo Medical University, Second Department of Surgery, Tochigi, Japan.
Kyung Hwa
KH
Park
Tokihiko
T
Sawada
Toru
T
Murakami
Yasuo
Y
Ishii
Mineko
M
Yasuo
Shohei
S
Fuchinoue
David M
DM
Goldenberg
Keiichi
K
Kubota
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D018920:Coculture Techniques; D005434:Flow Cytometry; D006084:Graft Rejection / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000517:prevention & control; D006684:HLA-DR Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D016377:Organ Transplantation; D017452:Receptors, IgG / Q000276:immunology; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013936:Thymidine / Q000378:metabolism; D014184:Transplantation, Homologous / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D017252:CD3 Complex; D019002:CD56 Antigen; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D013936:Thymidine