Improving the In Vivo Efficacy of an Anti-Tac (CD25) Immunotoxin by Pseudomonas Exotoxin A Domain II Engineering

• Published in: Molecular cancer therapeutics Vol. 17; no. 7; pp. 1486 - 1493
• Main Authors: Kaplan, Gilad, Mazor, Ronit, Lee, Fred, Jang, Youjin, Leshem, Yasmin, Pastan, Ira
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 01.07.2018
• Subjects: ADP Ribose Transferases - administration & dosage; ADP Ribose Transferases - genetics; ADP Ribose Transferases - immunology; Animals; Antibodies; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - immunology; Anticancer properties; Antitumor activity; Bacterial Toxins - administration & dosage; Bacterial Toxins - genetics; Bacterial Toxins - immunology; Biocompatibility; Cancer; CD22 antigen; CD25 antigen; Cell Line, Tumor; Cell Proliferation - drug effects; Cleavage; Clinical trials; Conformation; Cytotoxicity; Cytotoxicity, Immunologic - genetics; Effectiveness; Exotoxin A; Exotoxins - administration & dosage; Exotoxins - genetics; Exotoxins - immunology; Furin; Hematologic Neoplasms - drug therapy; Hematologic Neoplasms - genetics; Hematologic Neoplasms - immunology; Humans; Immunogenicity; Immunotoxins; Interleukin-2 Receptor alpha Subunit - antagonists & inhibitors; Interleukin-2 Receptor alpha Subunit - immunology; Lymphocytes T; Medical research; Mesothelin; Mice; Mutation; Point Mutation - genetics; Protein Domains - genetics; Protein Domains - immunology; Protein Engineering; Pseudomonas; Pseudomonas aeruginosa Exotoxin A; Sialic Acid Binding Ig-like Lectin 2 - antagonists & inhibitors; Sialic Acid Binding Ig-like Lectin 2 - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Toxicity; Virulence Factors - administration & dosage; Virulence Factors - genetics; Virulence Factors - immunology; Xenograft Model Antitumor Assays

Tac (CD25) is expressed on multiple hematologic malignancies and is a target for cancer therapies. LMB-2 is an extremely active anti-Tac recombinant immunotoxin composed of an Fv that binds to Tac and a 38-kDa fragment of exotoxin A (PE38). Although LMB-2 has shown high cytotoxicity toward Tac-expre...