Recombinant immunotoxins for treating cancer.
Recombinant immunotoxins are antibody-toxin chimeric molecules that kill cancer cells via binding to a surface antigen, internalization and delivery of the toxin moiety to the cell cytosol. In the cytosol, toxins catalytically inhibit a critical cell function and cause cell death. The antibody portion of the chimera targets antigens that are expressed preferentially on the surface of cancer cells. Truncated versions of either diphtheria toxin (DT) or Pseudomonas exotoxin (PE) can be used to construct fusions with cDNAs encoding antibody fragments or cell-binding ligands. Recombinant immunotoxins are routinely produced in E. coli and purified using standard chromatographic methods. Before they can be evaluated for anticancer activity in humans, recombinant immunotoxins undergo extensive preclinical testing. Immunotoxins must demonstrate cell-killing activity in tissue culture, antitumor activity in an animal model and have favorable pharmacokinetic and toxicity profiles. Candidate molecules with favorable characteristics are then evaluated in clinical trials. Here we report on the initial evaluation of BL22, a recombinant immunotoxin targeted to CD22 expressed on the surface of B-cell malignancies.
FitzGerald
David J
DJ
Laboratory of Molecular Biology, CCR, National Cancer Institute, Bethesda, MD 20892, USA. djpf@helix.nih.gov
Kreitman
Robert
R
Wilson
Wyndham
W
Squires
David
D
Pastan
Ira
I
D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D015815:Cell Adhesion Molecules; D002986:Clinical Trials as Topic; D004167:Diphtheria Toxin / Q000276:immunology / Q000627:therapeutic use; D005098:Exotoxins / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000627:therapeutic use; D007135:Immunoglobulin Variable Region / Q000276:immunology / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D000922:Immunotoxins / Q000276:immunology / Q000627:therapeutic use*; D037102:Lectins / Q000276:immunology; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D051918:Sialic Acid Binding Ig-like Lectin 2
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D004167:Diphtheria Toxin; D005098:Exotoxins; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D000922:Immunotoxins; D037102:Lectins; D011993:Recombinant Fusion Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2