title: 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.affiliation: Hughes Institute, St. Paul, Minnesota 55113, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Myers
authors.forename: X
authors.initials: X
authors.lastname: Jun
authors.forename: D
authors.initials: D
authors.lastname: Clementson
authors.forename: R
authors.initials: R
authors.lastname: Donelson
authors.forename: A
authors.initials: A
authors.lastname: Sicheneder
authors.forename: N
authors.initials: N
authors.lastname: Hoffman
authors.forename: K
authors.initials: K
authors.lastname: Bell
authors.forename: M
authors.initials: M
authors.lastname: Sarquis
authors.forename: M C
authors.initials: MC
authors.lastname: Langlie
authors.forename: N
authors.initials: N
authors.lastname: Turner
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D000911:Antibodies, Monoclonal; D019011:Antigens, CD7 / Q000276:immunology*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D000922:Immunotoxins / Q000302:isolation & purification / Q000627:therapeutic use*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000276:immunology*; D011786:Quality Control; D054789:Ribosome Inactivating Proteins, Type 1
chemical_list: D000911:Antibodies, Monoclonal; D019011:Antigens, CD7; D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein