TY - JOUR
T1 - A reevaluation of CD22 expression in human lung cancer
AU - Pop, Laurentiu M.
AU - Barman, Stephen
AU - Shao, Chunli
AU - Poe, Jonathan C.
AU - Venturi, Guglielmo M.
AU - Shelton, John M.
AU - Pop, Iliodora V.
AU - Gerber, David E.
AU - Girard, Luc
AU - Liu, Xiao Yun
AU - Behrens, Carmen
AU - Rodriguez-Canales, Jaime
AU - Liu, Hui
AU - Wistuba, Ignacio I.
AU - Richardson, James A.
AU - Minna, John D.
AU - Tedder, Thomas F.
AU - Vitetta, Ellen S.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer cells and cell lines express CD22, making it an important new therapeutic target for lung cancer. The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by quantitative real-time PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200 to 60,000-fold lower than those observed in the human CD22+ Burkitt lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by either CD22 antibodies or our highly potent anti-CD22 immunotoxin. In contrast, CD22 + Daudi cells expressed high levels of CD22mRNA and protein, and were sensitive to our CD22 immunotoxin. Importantly, primary non-small cell lung cancers from more than 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells, and that these cells cannot be killed by anti-CD22 immunotoxins.
AB - CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer cells and cell lines express CD22, making it an important new therapeutic target for lung cancer. The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by quantitative real-time PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200 to 60,000-fold lower than those observed in the human CD22+ Burkitt lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by either CD22 antibodies or our highly potent anti-CD22 immunotoxin. In contrast, CD22 + Daudi cells expressed high levels of CD22mRNA and protein, and were sensitive to our CD22 immunotoxin. Importantly, primary non-small cell lung cancers from more than 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells, and that these cells cannot be killed by anti-CD22 immunotoxins.
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U2 - 10.1158/0008-5472.CAN-13-1436
DO - 10.1158/0008-5472.CAN-13-1436
M3 - Article
C2 - 24395821
AN - SCOPUS:84892755101
SN - 0008-5472
VL - 74
SP - 263
EP - 271
JO - Cancer Research
JF - Cancer Research
IS - 1
ER -