Administration of an anti-CD5 immunoconjugate to patients with rheumatoid arthritis: effect on peripheral blood mononuclear cells and in vitro immune function.
OBJECTIVE
An immunoconjugate, CD5 Plus, composed of ricin A chain and murine IgG1 anti-CD5 monoclonal antibody is under investigation for treatment of rheumatoid arthritis. To understand better the mechanism of action of this agent, alterations in immune function and lymphocyte subpopulations were assessed in a subset of patients consecutively enrolled in 2-phase II clinical trials.


METHODS
Flow cytometric and in vitro functional analyses of peripheral blood mononuclear cells from 12 patients receiving 5 daily intravenous infusions of CD5 Plus at doses of 0.20 or 0.33 mg/kg were performed before, during and after treatment.


RESULTS
Peripheral CD3+ T cells were significantly depleted (p < 0.01) during treatment on Days 2 and 5 and returned towards baseline on Days 15 to 29; changes in CD5+ B cells occurred in parallel. There was no significant treatment effect on monocytes. All T cell subsets examined, including CD4, CD8, CD45RA, CD45RO, HLA-DR+, TCR-alpha beta and TCR-gamma delta, were affected equally through Day 15. On Day 29, the median CD4:CD8 ratio, elevated before treatment, was significantly decreased (p < 0.01), approaching the ratio observed in healthy controls. Proliferative responses to antigenic, allogeneic and mitogenic stimuli in vitro were depressed but detectable during the time of maximal T cell depletion and normalized to baseline values with recovery of T cell number. Spontaneous and pokeweed mitogen induced immunoglobulin secretion were unaffected in these patients.


CONCLUSIONS
Treatment associated effects of CD5 Plus were observed for both T and B cell populations which bear the CD5 antigen, and were reversible, as measured by in vitro assays of immune cell function, phenotype and number.
Fishwild
D M
DM
Department of Immunology, XOMA Corporation, Berkeley, CA.
Strand
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D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology / Q000628:therapy*; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D018956:CD5 Antigens; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000922:Immunotoxins / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D012276:Ricin / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018956:CD5 Antigens; D007074:Immunoglobulin G; D000922:Immunotoxins; D017452:Receptors, IgG; D012276:Ricin