Initiation of humoral and cellular immune responses in patients with refractory Hodgkin's disease by treatment with an anti-CD16/CD30 bispecific antibody.
Fifteen patients with refractory Hodgkin's disease were treated in a dose-escalation trial with the bispecific monoclonal antibody (bi-mAb) HRS-3/A9, which is directed against the Fc gamma receptor III (CD16 antigen) and the Hodgkin's-associated CD30 antigen. Treatment consisted of four cycles of four bi-mAb infusions given over 1 h every 3-4 days at different dose levels ranging from 1 mg/m2 to 64 mg/m2. Measurable serum levels (above 0.1 microgram/ml) of circulating bi-mAb could be detected in patients treated with doses above 4 mg/m2, reaching peak levels of 9.5 micrograms/ml immediately after the end of antibody infusion on the highest dose level. Bi-mAb elimination corresponded to second-order kinetics with a terminal half-life time (t1/2, beta) of 28-32 h. Bi-mAb treatment induced the occurrence of human anti-(mouse Ig) antibodies (HAMA) in 6 out of 13 patients initially testing negative. All 6 patients not only developed anti-isotypic anti-(mouse Ig) but also anti-idiotypic and anti-anti-idiotypic antibodies. While no consistent changes of peripheral blood cell counts, or of any lymphocyte subpopulation including natural killer (NK) cells, has been observed, 4 out of 6 evaluable patients treated with doses of at least 4 mg/m2 showed an increase of NK cell activity within 2 weeks after treatment, which lasted for a maximum of 12 weeks. Circulating amounts of soluble CD30 antigen could be detected in the serum of 6 patients. However, like the results and time courses of all the other immunological parameters evaluated, this was not predictive for treatment outcome.
Renner
C
C
Medizinische Klinik und Poliklinik, Universitätskliniken des Saarlandes, Homburg, Germany.
Hartmann
F
F
Jung
W
W
Deisting
C
C
Juwana
M
M
Pfreundschuh
M
M
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D018033:Antibodies, Bispecific / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000917:Antibody Formation; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology*; D001772:Blood Cell Count; D006689:Hodgkin Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007111:Immunity, Cellular; D017730:Ki-1 Antigen / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D017452:Receptors, IgG / Q000276:immunology*; D016879:Salvage Therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome
D000888:Antibodies, Anti-Idiotypic; D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017730:Ki-1 Antigen; D017452:Receptors, IgG