Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin's lymphoma.

Abstract

Anti-B-blocked ricin (anti-B4-bR) combines the specificity of the anti-B4 (CD19) monoclonal antibody with the protein toxin "blocked ricin." In blocked ricin, affinity ligands are attached to the ricin B-chain to attenuate its lectin binding capacity. In a phase I trial, Anti-B4-bR was administered by 7-day continuous infusion to 12 patients in complete remission after autologous bone marrow transplantation (ABMT) for relapsed B-cell non-Hodgkin's lymphoma (NHL). Patients were treated at 20, 40, and 50 micrograms/kg/d for 7 days. Potentially therapeutic serum levels could be sustained for 3 to 4 days. The maximum tolerated dose was 40 micrograms/kg/d for 7 days (total 280 micrograms/kg). The dose-limiting toxicities were reversible grade IV thrombocytopenia and elevation of hepatic transaminases. Mild capillary leak syndrome was manifested by hypoalbuminemia, peripheral edema (4 patients), and dyspnea (1 patient). Anti-immunotoxin antibodies developed in 7 patients. Eleven patients remain in complete remission between 13 and 26 months post-ABMT (median 17 months). These results show that Anti-B4-bR can be administered with tolerable, reversible toxicities to patients with B-cell NHL in complete remission following ABMT.

• Authors: M L Grossbard, J G Gribben, A S Freedman, J M Lambert, J Kinsella, S N Rabinowe, L Eliseo, J A Taylor, W A Blättler, C L Epstein
• Journal: Blood (Blood) Vol. 81 Issue 9 Pg. 2263-71 (May 01 1993) ISSN: 0006-4971 [Print] United States
• PMID: 8481509 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Anti-Idiotypic
• Antibodies, Monoclonal
• DNA, Neoplasm
• Immunotoxins
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• Ricin
• Protein-Tyrosine Kinases

Topics

• Antibodies, Anti-Idiotypic (blood)
• Antibodies, Monoclonal (therapeutic use, toxicity)
• Bone Marrow Transplantation
• Combined Modality Therapy
• DNA, Neoplasm (genetics, isolation & purification)
• Enzyme-Linked Immunosorbent Assay
• Follow-Up Studies
• Humans
• Immunotoxins (blood, therapeutic use, toxicity)
• Lymphoma, B-Cell (therapy)
• Polymerase Chain Reaction (methods)
• Protein-Tyrosine Kinases (genetics)
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogenes
• Ricin (blood, therapeutic use, toxicity)
• Transplantation, Autologous