Successful in vivo blockade of CD25 (high-affinity interleukin 2 receptor) on T cells by administration of humanized anti-Tac antibody to patients with psoriasis.
BACKGROUND
Daclizumab is a humanized antibody to the alpha-subunit (CD25) of the interleukin 2 (IL-2) receptor that blocks normal IL-2 binding to this receptor. Because IL-2 is a major stimulus for T-cell growth, blockade of the IL-2 receptor could be useful in treating T-cell-mediated (autoimmune) diseases.


OBJECTIVE
Our purpose was to determine whether adequate concentrations of antibody were achieved in circulating blood and in psoriatic skin lesions to saturate CD25 receptors. We also intended to measure clinical effect and safety of this agent when used alone (without other immunosuppressive drugs) in psoriasis.


METHODS
Nineteen patients with psoriasis in two centers received daclizumab at an initial dose of 2 mg/kg, then 1 mg/kg at weeks 2, 4, 8, and 12. To determine whether CD25 was blocked in vivo, flow cytometric studies measured (1) expression of CD25 on CD3(+) T cells derived from blood and (2) immuno-histochemistry measures of CD25(+) cells done on pretreatment and posttreatment biopsy specimens. Patients were followed up clinically with photographs and Psoriasis Area and Severity Index scores.


RESULTS
This study showed a consistent blockade of CD25 in peripheral blood and tissue during the first 4 weeks of therapy while the dosing was every 2 weeks. Variable desaturation of receptors began after 4 weeks, which correlated with a reversal in disease improvement. Patients with a pretreatment Psoriasis Area and Severity Index score of less than 36 showed a mean reduction in severity by 30% at 8 weeks (P =.02). During the 16 weeks of treatment, a 44.8% decrease in expression of the IL-2 receptor alpha-subunit was found. The absolute T-cell counts were calculated and showed no significant changes during the course of the study. No significant adverse events were produced by daclizumab during this study.


CONCLUSIONS
We therefore conclude that daclizumab is a well-tolerated agent that blocks CD25 expression in peripheral blood and skin. Furthermore, it may be useful in treating psoriasis in some patients.
Krueger
J G
JG
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10021-6399, USA. kruegej@rockvax.rockefeller.edu
Walters
I B
IB
Miyazawa
M
M
Gilleaudeau
P
P
Hakimi
J
J
Light
S
S
Sherr
A
A
Gottlieb
A B
AB
D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000187:drug effects* / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D000077561:Daclizumab