Towards optimal anti-Tac antibody dosing in the presence of antigenemia in adult T-cell leukemia-lymphoma (Meeting abstract). NLM AIDSLINE Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

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Towards optimal anti-Tac antibody dosing in the presence of antigenemia in adult T-cell leukemia-lymphoma (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 34:A2849 1993. Unique Identifier : AIDSLINE ICDB/93693792
Junghans RP; Goldman CK; Carrasquillo J; Reynolds J; Nelson DL; Waldmann TA; New England Deaconess Hosp., Boston, MA 02215

Abstract: Circulating antigen may interfere with antibody therapy by binding to antibody and reducing access to cellular targets. Patients with Tac+ leukemias and varying levels of circulating antigen (soluble Tac) were infused with anti-Tac antibody for therapy and imaging (Tac=IL2 receptor-alpha). With high soluble Tac levels, flow cytometry showed reduced anti-Tac binding to Tac+ cells in vivo, correlating with poorer imaging and a reduced 'fraction of unbound anti-Tac' (reduced antibody bioactivity) in patient sera, but which improved with larger antibody doses. The in vivo bioactivity of anti-Tac following infusion was compatible with a multiparameter model incorporating soluble Tac level, antibody dose, antibody t1/2, and a continuing rate of soluble Tac production. Based on these pharmacokinetic and bioactivity data, we derived a relation to predict doses of anti-Tac that overcome soluble antigen levels with minimum dilution of antibody radioactivity, thereby yielding improved antibody bioactivity, improved cell binding and improved targeting of radioactivity to tumor for imaging and therapy.
Keywords: Antibodies, Monoclonal/*THERAPEUTIC USE Antigens, Neoplasm/*IMMUNOLOGY Dose-Response Relationship, Drug Human HTLV-I Antigens/*IMMUNOLOGY Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/*IMMUNOLOGY/ THERAPY Receptors, Interleukin-2/*IMMUNOLOGY ABSTRACTKWDantibodies,monoclonal/KWDtherapeuticuseantigens,neoplasm/KWDimmunologydose-responserelationship,drughumanhtlv-iantigens/KWDimmunologyleukemia-lymphoma,t-cell,acute,htlv-i-associated/KWDimmunology/therapyreceptors,interleukin-2/KWDimmunologyabstract
930930
M9391188

Copyright © 1993 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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