Mesothelin, a possible target for immunotherapy, is expressed in primary AML cells.

Abstract

BACKGROUND:

Mesothelin is a promising candidate for tumor-specific therapy because of its limited expression in normal tissues and high expression in several cancers. The expression of the protein mesothelin in hematological malignancies has not yet been analyzed. SS1(dsFv)PE38 is a recombinant anti-mesothelin immunotoxin which is undergoing clinical evaluation in patients with mesothelin-expressing tumors.

METHODS AND RESULTS:

In this study we show that the mesothelin protein is expressed in leukemic cells from children with acute myeloid leukemia (AML). This finding was confirmed by western blot, immunocytochemistry and real time polymerase chain reaction (PCR). Despite the expression of mesothelin, the patient samples were not sensitive to immunotoxin SS1(dsFv)PE38 in MTT assays.

CONCLUSIONS:

Primary AML cells express mesothelin but SS1(dsFv)PE38 is not active in killing these cells. Other approaches that utilize mesothelin as a target might be more effective and should be tested against AML cells.

• Authors: Daniel Steinbach, Masanori Onda, Astrid Voigt, Kristin Dawczynski, Susan Wittig, Raffit Hassan, Bernd Gruhn, Ira Pastan
• Journal: European journal of haematology (Eur J Haematol) Vol. 79 Issue 4 Pg. 281-6 (Oct 2007) ISSN: 0902-4441 [Print] England
• PMID: 17803679 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• GPI-Linked Proteins
• Immunotoxins
• Membrane Glycoproteins
• Neoplasm Proteins
• SS1(dsFv)PE38
• Mesothelin

Topics

• Adolescent
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Blotting, Western
• Child
• Child, Preschool
• Drug Delivery Systems
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Female
• GPI-Linked Proteins
• Gene Expression Regulation, Leukemic (drug effects)
• Humans
• Immunohistochemistry
• Immunotherapy
• Immunotoxins (pharmacology, therapeutic use)
• Infant
• Leukemia, Myeloid, Acute (genetics, immunology, metabolism, pathology, therapy)
• Male
• Membrane Glycoproteins (antagonists & inhibitors, biosynthesis)
• Mesothelin
• Neoplasm Proteins (antagonists & inhibitors, biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction