Large scale manufacturing of TXU(anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate for clinical trials.

Abstract

We have conjugated the murine monoclonal anti-CD7 antibody TXU to the plant hemitoxin pokeweed antiviral protein (PAP) to construct an effective immunotoxin against CD7 antigen positive hematologic malignancies. The scaled-up production and purification of TXU antibody, PAP toxin, and TXU-PAP immunotoxin permitted the manufacturing of a highly purified clinical-grade TXU-PAP preparation. In clonogenic assays, TXU-PAP elicited selective and potent cytotoxicity against CD7 antigen positive human leukemia cells and killed primary clonogenic leukemic cells from T-lineage acute lymphoblastic leukemia (ALL) patients. To our knowledge, this pre-IND work represents the first effort of producing a clinical-grade PAP immunotoxin for treatment of T-lineage ALL. Since the CD7 antigen is also expressed on AML cells, TXU-PAP could also be useful for the treatment of CD7 positive acute myeloid leukemia (AML) patients.

• Authors: D E Myers, X Jun, D Clementson, R Donelson, A Sicheneder, N Hoffman, K Bell, M Sarquis, M C Langlie, N Turner, F M Uckun
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 27 Issue 3-4 Pg. 275-302 (Oct 1997) ISSN: 1042-8194 [Print] United States
• PMID: 9402326 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD7
• Antineoplastic Agents, Phytogenic
• Immunotoxins
• Plant Proteins
• Ribosome Inactivating Proteins, Type 1
• N-Glycosyl Hydrolases
• pokeweed antiviral protein

Topics

• Antibodies, Monoclonal
• Antigens, CD7 (immunology)
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Clinical Trials as Topic
• Humans
• Immunotoxins (isolation & purification, therapeutic use)
• Leukemia-Lymphoma, Adult T-Cell (drug therapy)
• N-Glycosyl Hydrolases
• Plant Proteins (immunology)
• Quality Control
• Ribosome Inactivating Proteins, Type 1