Large Scale Manufacturing of TXU(Anti-CD7)-Pokeweed Antiviral Protein (PAP) Immunoconjugate for Clinical Trials

• Published in: Leukemia & lymphoma 1997, Vol.27 (3-4), p.275-302
• Main Authors: Myers, Dorothea E., Jun, Xiao, Clementson, Dina, Donelson, Randy, Sicheneder, Andrew, Hoffman, Nathan, Bell, Kim, Sarquis, Mireille, Langlie, Mridula-Chandan, Turner, Nilgun, Uckun, Fatih M.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal; Antigens, CD7 - immunology; Antineoplastic Agents, Phytogenic - therapeutic use; clinical trials; Clinical Trials as Topic; Humans; Immunotoxins - isolation & purification; Immunotoxins - therapeutic use; Leukemia-Lymphoma, Adult T-Cell - drug therapy; Manufacturing of immunoconjugate; N-Glycosyl Hydrolases; Plant Proteins - immunology; Pokeweed anti-viral protein (PAP); Quality Control; Ribosome Inactivating Proteins, Type 1; TXU (anti-CD7)
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428199709059683

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.