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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
- 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.
- Subjects :
- Cancer Research
medicine.drug_class
medicine.medical_treatment
Lymphocyte
Immunology
Ki-1 Antigen
Monoclonal antibody
Natural killer cell
Mice
Antigen
Antibody Specificity
Antigens, Neoplasm
T-Lymphocyte Subsets
Antibodies, Bispecific
medicine
Animals
Humans
Immunology and Allergy
Lymphocyte Count
Salvage Therapy
Immunity, Cellular
Bispecific monoclonal antibody
biology
business.industry
Receptors, IgG
Immunotherapy
Hodgkin's lymphoma
medicine.disease
Hodgkin Disease
Antibodies, Anti-Idiotypic
Blood Cell Count
Killer Cells, Natural
Treatment Outcome
medicine.anatomical_structure
Oncology
Antibody Formation
biology.protein
Antibody
business
Subjects
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