A pilot study of anti-CD5 ricin A chain immunoconjugate in systemic lupus erythematosus.
OBJECTIVE
To determine the safety and clinical and biological effects of a murine monoclonal anti-CD5 ricin A chain immunoconjugate (CD5 Plus) in patients with systemic lupus erythematosus (SLE).


METHODS
An open label phase I study of CD5 Plus. A dose of 0.1 mg/kg was administered intravenously on 5 consecutive days. A second course of immunoconjugate was given to patients who failed to show any clinical response one to 2 months later.


RESULTS
Six patients (4 with glomerulonephritis and 2 with thrombocytopenia) were studied. Improvement was documented in 2 patients with nephritis; no effect on thrombocytopenia was observed. Adverse effects were mild and transient. Relative to pretreatment lymphocyte counts, the mean reduction in CD3+ T cell count was 69% at 2 weeks, 32% at one month, and 34% at 6 months following initial treatment. A comparable decrease in all subpopulations of mature T cells was noted, using a variety of surface markers, including CD4 and CD8. The mean percentage of T cells expressing the activation markers HLA-DR and interleukin 2R (IL-2R) was high before treatment, and remained so. There was a transient decrease in CD5+ B cells, but no persistent depletion of total B cell numbers. There was no consistent change in natural killer cell populations.


CONCLUSIONS
Anti-CD5 ricin A chain immunoconjugate is well tolerated in patients with SLE, causes modest T cell depletion which may persist for months, and may have some clinical efficacy in lupus nephritis.
Stafford
F J
FJ
Arthritis and Rheumatism Branch (ARB), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD 20892.
Fleisher
T A
TA
Lee
G
G
Brown
M
M
Strand
V
V
Austin
H A
HA
Balow
J E
JE
Klippel
J H
JH
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes; D018956:CD5 Antigens; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008181:Lupus Nephritis / Q000628:therapy*; D018655:Lymphocyte Count; D008297:Male; D010865:Pilot Projects; D010976:Platelet Count; D012276:Ricin / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018956:CD5 Antigens; D018796:Immunoconjugates; D000922:Immunotoxins; C068230:zolimomab aritox; D012276:Ricin