Initiation of humoral and cellular immune responses in patients with refractory Hodgkin's disease by treatment with an anti-CD16/CD30 bispecific antibody |
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Authors: | Christoph Renner Frank Hartmann Wolfram Jung Christina Deisting Marieta Juwana Michael Pfreundschuh |
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Institution: | Medizinische Klinik und Poliklinik, Innere Medizin I, Universit?tskliniken des Saarlandes, D-66421 Homburg, Germany Tel.: +49-6841-16-3084 Fax: +49-6841-16-3004, DE
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Abstract: | 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 Fcγ 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 μg/ml) of circulating bi-mAb could be detected in patients treated with doses above 4 mg/m2, reaching peak levels of 9.5 μg/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 (t
1/2,β) 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.
Received: 16 September 1999 / Accepted: 6 January 2000 |
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Keywords: | Immunotherapy Monoclonal antibodies Hodgkin's lymphoma |
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