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

Leuk Lymphoma. 1997 Oct;27(3-4):275-302. doi: 10.3109/10428199709059683.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

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

Substances

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