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Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: results of a pilot, multicenter, multiple-dose, placebo-controlled study.
J Am Acad Dermatol
October 2000
Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
Background: OKTcdr4a (IMUCLONE) is a humanized anti-CD4 IgG4 monoclonal antibody that retains the binding and in vitro immunosuppressive properties of the parent murine antibody. Psoriasis is a chronic disease for which treatment with multiple doses of monoclonal antibodies is likely to be required for adequate control.
Objective: This study was performed to test the efficacy and safety of OKTcdr4a, given in sequential courses over a period of several weeks, in the treatment of moderate to severe psoriasis vulgaris.
Potent anti-HIV (type 1 and type 2) activity of polyoxometalates: structure-activity relationship and mechanism of action.
J Med Chem
March 2000
Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium, USA.
A series of polyoxometalates have been synthesized and evaluated for their inhibitory effects on HIV-1(III(B)) and HIV-1(ROD) replication in MT-4 cells. All compounds showed activity against HIV-1 and HIV-2, but the antiviral potency of the heteropolytungstates varied considerably depending on their chemical structure. The antiviral activity of single, double, and triple Keggin-type of compounds against HIV-1(III(B)) replication was comparable (IC(50): 0.
View Article and Find Full Text PDFThe expansion of human gammadelta T cells in response to Daudi cells requires the participation of CD4+ T cells.
Immunology
June 1999
Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA.
The Burkitt's lymphoma cell line Daudi is a potent inducer of human gammadelta T-cell expansion. Using an in vitro culture system comprised of irradiated Daudi cells as stimulators and normal human lymphocytes as responders, the cellular determinants of this response were investigated. Three of four monoclonal antibodies (mAbs 1-1C4, L243, and 9.
View Article and Find Full Text PDFRole of the beta-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia.
J Virol
April 1998
Center for Neurovirology and Neurodegenerative Disorders and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198, USA.
Human immunodeficiency virus type 1 (HIV-1) infection in mononuclear phagocyte lineage cells (monocytes, macrophages, and microglia) is a critical component in the pathogenesis of viral infection. Viral replication in macrophages serves as a reservoir, a site of dissemination, and an instigator for neurological sequelae during HIV-1 disease. Recent studies demonstrated that chemokine receptors are necessary coreceptors for HIV-1 entry which determine viral tropism for different cell types.
View Article and Find Full Text PDFHumanized IgG1 and IgG4 anti-CD4 monoclonal antibodies: effects on lymphocytes in the blood, lymph nodes, and renal allografts in cynomolgus monkeys.
Transplantation
March 1998
Massachusetts General Hospital, and the Department of Pathology, Harvard Medical School, Boston 02114, USA.
Background: Optimizing therapeutic monoclonal antibody (mAb) depends on the incorporation of the necessary effector functions and the development of hypoantigenic "humanized" antibodies by genetic engineering, which then need to be tested in appropriate preclinical trials.
Methods: Constructs of humanized OKT4A containing the complementarity-determining region (CDR) of murine OKT4A and the framework and constant regions of human light (kappa) and heavy chains (IgG1 and IgG4) were prepared and tested in cynomolgus monkeys who received a renal allograft. A prophylactic course of CDR-OKT4A/human (h) IgG1 or CDR-OKT4A/ hIgG4, either as high-dose single bolus (10 mg/kg) or as low-dose multiple infusion (1 mg/kg for 12 days) was given, and the effects on graft survival, immunohistology, circulating cells, and lymph node cells were assessed.
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