Anti-CD16/CD30 bispecific antibodies as possible treatment for refractory Hodgkin's disease.

Abstract

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.

• Authors: F Hartmann, C Renner, W Jung, M Pfreundschuh
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 31 Issue 3-4 Pg. 385-92 (Oct 1998) ISSN: 1042-8194 [Print] United States
• PMID: 9869203 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bispecific
• Ki-1 Antigen
• Receptors, IgG

Topics

• Adult
• Animals
• Antibodies, Bispecific (administration & dosage, adverse effects, immunology)
• Dose-Response Relationship, Drug
• Female
• Hodgkin Disease (drug therapy, immunology)
• Humans
• Immunotherapy
• Ki-1 Antigen (immunology)
• Killer Cells, Natural (immunology)
• Lymphocyte Activation
• Male
• Mice
• Middle Aged
• Receptors, IgG (immunology)