HuMax-CD4

Abstract

Background: Psoriasis is characterized by infiltration with mononuclear cells. Especially activated memory CD4 + T cells are critical in the pathogenesis. Interaction between the CD4 receptor and the major histocompatibility complex class II molecule is important for T-cell activation. Objective: To test safety and efficacy of a fully human monoclonal anti-CD4 antibody (HuMax-CD4) in the treatment of psoriasis. Design: Multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients: Eighty-five patients with moderate to severe psoriasis. Interventions: Subcutaneous infusions of placebo or HuMax-CD4 at doses of 20, 80, 160, or 280 mg once weekly for 4 weeks. Main Outcome Measures: Psoriasis Area and Severity Index (PASI), investigators' and patients' overall response assessment, adverse events, laboratory assessment including total T-cell and subtype counts, CD4 receptor occupancy, and interleukin 2 receptor levels. Results: At week 7, mean PASI was reduced in all treatment groups (95% confidence intervals are in parentheses): placebo, 8% (−3% to 19%); 20 mg, 12% (−6% to 27%); 80 mg, 14% (−14% to 35%); 160 mg, 16% (−4% to 33%); and 280 mg, 24% (−10% to 48%). At the highest dose level, 6 (38%) of 16 patients obtained more than 25% reduction of PASI and 3 (19%) obtained more than 50% reduction of PASI. A dose-dependent decrease in total lymphocyte count was seen and was parallel to a dose-dependent decrease in CD4 + T cells. This decrease was due to a decrease in the memory subset, whereas the naive subset was affected to a minor degree. Four weeks of treatment with HuMax-CD4 was safe and well tolerated. Conclusions: Treatment with HuMax-CD4 led to a moderate, not statistically significant reduction in PASI. The efficacy results obtained after only 4 weeks of treatment suggest that longer treatment would lead to even further reduction of PASI.

Protective versus pathogenic anti-CD4 immunity: insights from the study of natural resistance to HIV infection

“…implies modification of functional effects of the original reagent. Recently, a fully human anti-CD4 monoclonal antibody (HuMax-CD4) was tested in a multicenter, double blind, placebo-controlled, randomized clinical trial on 85 moderate to severe psoriasis patients, showing decreases in the psoriasis skin score, although this failed to reach statistical significance [41]. …”

Transient CD4+ T cell depletion during suppressive ART reduces the HIV reservoir in humanized mice

“…Significantly lower levels of human CD45 + cells and CD3 + T cells were observed in treated mice compared with controls at day 3 (CD45 + cells, p = 0.0381; CD3 + T cells, p = 0.0191) while no significant differences were observed at days 10, 17, 23, 30 and 36 (Fig 2B and 2C). In contrast, the frequency of CD19 + human B cell was significantly higher in anti-CD4 antibody-treated animals compared with control animals at day 3 (p = 0.0191) but not at days 10,17,23,30 and 36 (Fig 2D).…”

“…Unlike anti-HIV broadly neutralizing antibodies (bNAbs) and other HIV-targeted immunotherapies in development, anti-CD4 antibody-mediated depletion of CD4 + T cells does not require the induction of viral antigen expression. Anti-CD4 antibody treatment has been used for treating various human diseases in clinical trials; in which the depletion of CD4 + T cells was reversible, well-tolerated, and generally with no clinical evidence of immunosuppression [9][10][11][12].…”

Management of cutaneous T cell lymphoma: new and emerging targets and treatment options

“…Zanolimumab (Hu-Max CD4) is a humanized anti-CD4 monoclonal antibody that has been shown in vitro to mediate antibody-dependent cellular cytotoxicity, primarily in CD4 + CD45RO + T cells 131. Zanolimumab also blocks T cell activation by macrophages in Pautrier’s micro abscesses via induction of inhibitory signaling pathways involving SHIP-1 and DOK-1 132.…”