title: A reevaluation of CD22 expression in human lung cancer.
abstract: 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 CD22 mRNA 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.
authors.affiliation: Authors' Affiliations: Cancer Immunobiology Center and Hamon Center for Therapeutic Oncology Research; Departments of Immunology, Internal Medicine, Microbiology, Pathology, and Pharmacology, University of Texas Southwestern Medical Center, Dallas; Departments of Thoracic/Head and Neck Medical Oncology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston; Bio-Synthesis Inc., Lewisville, Texas; and Department of Immunology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Laurentiu M
authors.initials: LM
authors.lastname: Pop
authors.forename: Stephen
authors.initials: S
authors.lastname: Barman
authors.forename: Chunli
authors.initials: C
authors.lastname: Shao
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Poe
authors.forename: Guglielmo M
authors.initials: GM
authors.lastname: Venturi
authors.forename: John M
authors.initials: JM
authors.lastname: Shelton
authors.forename: Iliodora V
authors.initials: IV
authors.lastname: Pop
authors.forename: David E
authors.initials: DE
authors.lastname: Gerber
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.forename: Xiao-yun
authors.initials: XY
authors.lastname: Liu
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Jaime
authors.initials: J
authors.lastname: Rodriguez-Canales
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Vitetta
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000276:immunology / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D012333:RNA, Messenger; D051918:Sialic Acid Binding Ig-like Lectin 2