A reevaluation of CD22 expression in human lung cancer
Laurentiu M Pop1, Stephen Barman, Chunli Shao
1Authors' 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.
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.
Insights
CD22 is not expressed on lung cancer cells, contrary to previous reports. Therefore, CD22-targeted immunotoxins are ineffective for treating lung cancer, as validated by extensive preclinical testing.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- CD22 is a transmembrane glycoprotein on B cells that inhibits B-cell receptor signaling.
- Previous studies suggested CD22 expression on lung cancer cells, identifying it as a potential therapeutic target.
- The efficacy of CD22-targeted immunotoxins for lung cancer treatment requires independent validation.
Purpose of the Study:
- To validate CD22 expression in human lung cancer cell lines and primary tumors.
- To assess the therapeutic potential of CD22 immunotoxins against lung cancer.
- To investigate the role of CD22 in lung cancer cell proliferation.
Main Methods:
- Quantitative real-time PCR to measure CD22 mRNA levels.
- Flow cytometry and Western blot analysis for CD22 protein detection.
- Immunohistochemistry on patient specimens.
- In vitro proliferation assays with CD22 antibodies and immunotoxins.
Main Results:
- Lung cancer cell lines exhibited significantly lower CD22 mRNA levels compared to CD22(+) Daudi cells.
- No detectable surface or intracellular CD22 protein was found in lung cancer cell lines.
- CD22 antibodies and immunotoxins did not affect lung cancer cell proliferation.
- Primary non-small cell lung cancers showed no detectable CD22 protein expression.
- CD22(+) Daudi cells were sensitive to CD22 immunotoxin treatment.
Conclusions:
- CD22 is not expressed at measurable levels on lung cancer cells or primary tumors.
- Lung cancer cells are not susceptible to anti-CD22 immunotoxin therapy.
- Previous findings on CD22 expression in lung cancer require re-evaluation.
