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Initiation of humoral and cellular immune responses in patients with refractory Hodgkin's disease by treatment with an anti-CD16/CD30 bispecific antibody

Authors :
Wolfram Jung
Marieta Juwana
Frank Hartmann
Michael Pfreundschuh
Christina Deisting
Christoph Renner
Source :
Cancer Immunology, Immunotherapy. 49:173-180
Publication Year :
2000
Publisher :
Springer Science and Business Media LLC, 2000.

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 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.

Details

ISSN :
14320851 and 03407004
Volume :
49
Database :
OpenAIRE
Journal :
Cancer Immunology, Immunotherapy
Accession number :
edsair.doi.dedup.....7af1af22b708dd871a0d2a0849844453
Full Text :
https://doi.org/10.1007/s002620050617