Anti-CD16/CD30 bispecific antibodies as possible treatment for refractory Hodgkin's disease.
Fifteen patients with refractory Hodgkin's disease were treated in a phase I/II dose escalation trial with the NK-cell activating bispecific monoclonal antibody HRS-3/A9 which is directed against the Fcgamma-receptor III (CD16 antigen) and the Hodgkin's associated CD30 antigen, respectively. HRS-3/A9 was given four times every 3-4 days starting with 1 mg/m2. The treatment was well tolerated and the maximum tolerated dose was not reached at 64 mg/m2, the highest dose given due to limited amounts of HRS-3/A9 available. Mild to moderate side effects occured in six patients and consisted of fever, pain in involved lymph nodes, and a maculopapulous rash. Median counts of NK-cells and of all lymphocyte subsets were considerably decreased in the patients before therapy and showed no consistent changes under therapy. Eight patients developed human anti-mouse immunoglobulin antibodies, and five patients showed an allergic reaction after attempted retreatment. One complete and one partial remission (lasting 6 and 3 months, respectively), three minor responses (lasting 1 to 15 months), two disease stabilizations (for 2 and 17 months, respectively), and one mixed response were achieved. There was no clearcut dose-side effect or dose-response correlation. Our results encourage further clinical trials with this novel immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the murine bispecific antibodies.
Hartmann
F
F
Medizinische Klinik I, Universitätskliniken des Saarlandes, Homburg, Germany.
Renner
C
C
Jung
W
W
Pfreundschuh
M
M
D000328:Adult; D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D017730:Ki-1 Antigen / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008875:Middle Aged; D017452:Receptors, IgG / Q000276:immunology*
D018033:Antibodies, Bispecific; D017730:Ki-1 Antigen; D017452:Receptors, IgG