title: Effects of the intermolecular toxin-monoclonal antibody linkage on the in vivo stability, immunogenicity and anti-leukemic activity of B43 (anti-CD19) pokeweed antiviral protein immunotoxin.
abstract: We have successfully constructed highly potent and selective anti-CD19 PAP immunotoxins using each of the three crosslinking agents, SPDP, LC-SPDP, or SMPT, to generate an intermolecular bridge between the B43 MoAb and PAP toxin moieties. These immunotoxins were selectively immunoreactive with and cytotoxic against CD19+ B-lineage ALL cells. In this report, we compared (a) in vivo chemical, immunological, and biological stability, (b) in vivo immunogenicity, and (c) in vivo anti-leukemic activity of various B43-PAP immunotoxin constructs. Our data recommend the use of SPDP and SMPT rather than LC-SPDP for generation of B43(anti-CD19)-PAP immunotoxins as clinical anti-leukemic agents. To our knowledge, this is the first comparative analysis of the in vivo pharmacokinetic features, immunogenicity, and anti-leukemic activity of anti-CD19 PAP immunotoxins that were prepared with different heterobifunctional crosslinking agents.
authors.affiliation: Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis.
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
authors.forename: D E
authors.initials: DE
authors.lastname: Myers
authors.forename: J D
authors.initials: JD
authors.lastname: Irvin
authors.forename: V M
authors.initials: VM
authors.lastname: Kuebelbeck
authors.forename: D
authors.initials: D
authors.lastname: Finnegan
authors.forename: L M
authors.initials: LM
authors.lastname: Chelstrom
authors.forename: L L
authors.initials: LL
authors.lastname: Houston
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology*; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D004355:Drug Stability; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011817:Rabbits; D054789:Ribosome Inactivating Proteins, Type 1; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein