Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients.

Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients. Abstract Text:

Masanori Onda,Satoshi Nagata,David J FitzGerald,Richard Beers,Robert J Fisher,James J Vincent,Byungkook Lee,Michihiro Nakamura,Jaulang Hwang,Robert J Kreitman,Raffit Hassan,Ira Pastan,

Recombinant immunotoxins composed of an Ab Fv fragment joined to a truncated portion of Pseudomonas exotoxin A (termed PE38) have been evaluated in clinical trials for the treatment of various human cancers. Immunotoxin therapy is very effective in hairy cell leukemia and also has activity in other hemological malignancies; however, a neutralizing Ab response to PE38 in patients with solid tumors prevents repeated treatments to maximize the benefit. In this study, we analyze the murine Ab response as a model to study the B cell epitopes associated with PE38. Sixty distinct mAbs to PE38 were characterized. Mutual competitive binding of the mAbs indicated the presence of 7 major epitope groups and 13 subgroups. The competition pattern indicated that the epitopes are discrete and could not be reproduced using a computer simulation program that created epitopes out of random surface residues on PE38. Using sera from immunotoxin-treated patients, the formation of human Abs to each of the topographical epitopes was demonstrated. One epitope subgroup, E1a, was identified as the principal neutralizing epitope. The location of each epitope on PE38 was determined by preparing 41 mutants of PE38 in which bulky surface residues were mutated to either alanine or glycine. All 7 major epitope groups and 9 of 13 epitope subgroups were identified by 14 different mutants and these retained high cytotoxic activity. Our results indicate that a relatively small number of discrete immunogenic sites are associated with PE38, most of which can be eliminated by point mutations.

Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients. Publishing Authors By Initials

M Onda,S Nagata,DJ FitzGerald,R Beers,RJ Fisher,JJ Vincent,B Lee,M Nakamura,J Hwang,RJ Kreitman,R Hassan,I Pastan,

For similar biological factors: toxins, biological: virulence factors research abstracts see: biological factors: toxins, biological: virulence factors research

PUBMED ID PMID:

MEDLINE DATE:

Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 177

Page Numbers: 8822-34

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Dec

YEAR: 2006

Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients. Keywords Mesh Terms:

KEYWORDS: Virulence Factors

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients. Information

Substance Name: toxA protein, Pseudomonas aeruginosa

Registry Number: EC 2.4.2.31

Grant and Affiliation Information for Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients.

AFFILIATION: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.

Country: United States

AGENCY: United States NCI

GRANT: N01 CO 12400

ACRONYM: CO

MEDLINETA: J Immunol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin PE38 used to make immunotoxins for the treatment of cancer patients Related Publications

• A model for obesity and gigantism due to disruption of the Ankrd26 gene.
• An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes.
• Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients.
• Dialysis facility characteristics and variation in employment rates: a national study.
• Differential Cellular Internalization of Anti-CD19 and -CD22 Immunotoxins Results in Different Cytotoxic Activity.
• Expression of POTE protein in human testis detected by novel monoclonal antibodies.
• FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia, and B-cell non-Hodgkin lymphoma as a target of immunotoxins.
• Immunotoxin and Taxol synergy results from a decrease in shed mesothelin levels in the extracellular space of tumors.
• Mesothelin, a possible target for immunotherapy, is expressed in primary AML cells.
• Novel genes in the PAGE and GAGE family of tumor antigens found by homology walking in the dbEST database.
• Palmitoylation of POTE family proteins for plasma membrane targeting.
• Selective POTE Paralogs on Chromosome 2 are Expressed in Human Embryonic Stem Cells.
• Synergistic antitumor activity of taxol and immunotoxin SS1P in tumor-bearing mice.
• Topology of NGEP, a Prostate-Specific Cell:Cell Junction Protein Widely Expressed in Many Cancers of Different Grade Level.