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.
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: Min Li; Uddalak Bharadwaj; Rongxin Zhang; Sheng Zhang; Hong Mu; William E Fisher; F Charles Brunicardi; Changyi Chen; Qizhi Yao Journal: Mol Cancer Ther Date: 2008-02 Impact factor: 6.261
Authors: Bei Wang; Janelle M Y Kuroiwa; Li-Zhen He; Anna Charalambous; Tibor Keler; Ralph M Steinman Journal: Ann N Y Acad Sci Date: 2009-09 Impact factor: 5.691
Authors: Allison J Kaeding; Sonali P Barwe; Anilkumar Gopalakrishnapillai; Rhonda E Ries; Todd A Alonzo; Robert B Gerbing; Colin Correnti; Michael R Loken; Lisa Eidenschink Broderson; Laura Pardo; Quy H Le; Thao Tang; Amanda R Leonti; Jenny L Smith; Cassie K Chou; Min Xu; Tim Triche; Steven M Kornblau; E Anders Kolb; Katherine Tarlock; Soheil Meshinchi Journal: Blood Adv Date: 2021-05-11