Identification and elimination of an immunodominant T-cell epitope in recombinant immunotoxins based on Pseudomonas exotoxin A

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 51; pp. E3597 - E3603
• Main Authors: Mazor, Ronit, Vassall, Aaron N., Eberle, Jaime A., Beers, Richard, Weldon, John E., Venzon, David J., Tsang, Kwong Y., Benhar, Itai, Pastan, Ira
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.12.2012; National Acad Sciences
• Series: PNAS Plus
• Subjects: ADP Ribose Transferases - chemistry; alanine; alleles; Amino acids; Antibodies - chemistry; antibody formation; Bacterial proteins; bacterial toxins; Bacterial Toxins - chemistry; Biological Sciences; CD4-Positive T-Lymphocytes - cytology; Correlation analysis; cytotoxicity; Enzyme-Linked Immunosorbent Assay - methods; Epitopes - chemistry; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; exotoxins; Exotoxins - chemistry; Gene Deletion; Genetic Variation; Humans; Immune System; immunodominant epitopes; Immunotoxins; interleukin-2; Interleukin-2 - metabolism; Leukocytes, Mononuclear - cytology; Molecular Conformation; mutants; neoplasms; neutralizing antibodies; patients; Peptides - chemistry; PNAS Plus; Protein Binding; Protein Conformation; Protein Engineering - methods; Protein Structure, Tertiary; Proteins; Pseudomonas; Pseudomonas aeruginosa Exotoxin A; recombinant fusion proteins; T cell receptors; T-lymphocytes; therapeutics; Toxins; Virulence Factors - chemistry

Recombinant immunotoxins (RITs) are chimeric proteins that are being developed for cancer treatment. We have produced RITs that contain PE38, a portion of the bacterial protein Pseudomonas exotoxin A. Because the toxin is bacterial, it often induces neutralizing antibodies, which limit the number of...