Anti-idiotypic monoclonal antibody to a T-cell chronic lymphatic leukemia. Characterization of the antibody, in vitro effector functions and results of therapy.
A murine anti-idiotypic monoclonal antibody (mAb), F1, (IgG2a) was produced against the variable part of the T-cell receptor for antigen (Ti, alpha/beta) on the tumor cells of a patient with T-cell chronic lymphatic leukemia (CD3+,8+,4-). The molecular weight of the protein reactive with mAb F1, comodulation and coprecipitation with anti-CD3 antibody, and the restricted tumor-cell reactivity strongly support the anti-idiotypic nature of mAb F1. MAb F1 also stained less than or equal to 4% of peripheral blood lymphocytes of healthy donors. MAb F1 did not stimulate the tumor cells to DNA synthesis, but stimulated a fraction of the normal peripheral blood lymphocytes, mAb F1 did not mediate antibody-dependent cellular cytotoxicity or complement lysis to any significant degree in vitro. Three infusion of 1-10 mg anti-idiotypic mAb were given over a period of 4 weeks. The plasma half-life for mAb F1 was 3 h in the first 2 h after infusion and 44 h from 2 h to 120 h after infusion. After each treatment a rapid decrease of circulating tumor cells was seen. During the observation period an 80% reduction of the total circulating tumor cells was noted. After the second infusion, IgM and IgG antimouse antibodies were detected. Side-effects from therapy were fever, chills, nausea, vomiting, diarrhea, tachycardia, increase in systolic blood pressure and shortness of breath. Thus, in T-cell malignancies a major reduction of circulating tumor cells can be accomplished by low doses of anti-idiotypic mAb. Anti-idiotypic mAb might be a therapeutic agent of significant importance.
Janson
C H
CH
Department of Immunology, Karolinska Institute, Stockholm, Sweden.
Tehrani
M J
MJ
Mellstedt
H
H
Wigzell
H
H
D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000032:analysis* / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000032:analysis* / Q000502:physiology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000096:biosynthesis / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D015461:Leukemia, Prolymphocytic, T-Cell / Q000097:blood / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007130:Immunoglobulin Idiotypes; D011948:Receptors, Antigen, T-Cell