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(TM), composed of ricin A chain and murine IgG1 anti-CD5 monoclonal antibody is under investigation f or treatment of rheumatoid arthritis. To understand better the mechani sm of action of this agent, alterations in immune function and lymphoc yte subpopulations were assessed in a subset of patients consecutively enrolled in 2-phase II clinical trials.Methods. Flow cytometric and i n vitro functional analyses of peripheral blood mononuclear cells from 12 patients receiving 5 daily intravenous infusions of CD5 Plus at do ses of 0.20 or 0.33 mg/kg were performed before, during and after trea tment. Results. Peripheral CD3+ T cells were significantly depleted (p < 0.01) during treatment on Days 2 and 5 and returned towards baselin e on Days 15 to 29; changes in CD5+ B cells occurred in parallel. Ther e 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 significantl y decreased (p < 0.01), approaching the ratio observed in healthy cont rols. Proliferative responses to antigenic, allogeneic and mitogenic s timuli in vitro were depressed but detectable during the time of maxim al T cell depletion and normalized to baseline values with recovery of T cell number. Spontaneous and pokeweed mitogen induced immunoglobuli n secretion were unaffected in these patients. Conclusion. Treatment a ssociated effects of CD5 Plus were observed for both T and B cell popu lations which bear the CD5 antigen, and were reversible, as measured b y in vitro assays of immune cell function, phenotype and number.