IADR Abstract Archives
Overexpression of Tumor Antigen Neurotrimin (NTM) in Oral Cancer
Objectives: Oral cancer is the most common type of head and neck cancer. While many early stage tumors can be treated, advanced stage survival rate is 30%, indicating a need for new treatment modalities. Chimeric Antigen Receptor T-Cell (CAR-T) therapy is an immunotherapy in which the patient’s own T-cells are engineered to target tumors. However, candidates for CAR-T targets in oral cancer have not been explored systematically. The aim of this study is to characterize the expression pattern and cellular localization of neurotrimin (NTM) protein as a candidate CAR-T target for oral cancer treatment.
Methods: To identify potential CAR-T target antigens, data from the Cancer Genomic Atlas were analyzed, comparing gene expression in oral tumors versus corresponding adjacent healthy tissues. To validate tumor antigen expression, three oral cancer cell lines (OQ01, HN, CAL27), an oral epithelial cell line (HOK) and 12 tumor specimens were analyzed by immunofluorescence. Oral tumor biopsies were stained with NTM antibody following antigen retrieval.
Results: NTM was overexpressed 6.4-fold in 303 oral cancer patient tissues versus healthy control tissues. All cell lines stained positively for NTM, with OQ01 demonstrating the strongest expression. NTM was localized mainly to the cytoplasm and cell surface, with heterogeneous patterns of expression between cell lines. Moreover, 11 out of 12 oral tumor biopsies were positively stained and one specimen clearly demonstrated cell surface expression of NTM.
Conclusions: NTM expression showed heterogeneity in cancer cell lines and tumor specimens, demonstrating that this protein is a potential target antigen for CAR-T immunotherapy for some oral cancer patients. NTM is a glycosylphosphatidylinositol (GPI)-anchored adhesion molecule forming surface complexes that influence neurite growth. GPI-anchored proteins have been described as biomarkers for several cancers, including overexpression in epithelial ovarian tumors. Further work is ongoing to determine whether NTM is a suitable CAR-T target.
Methods: To identify potential CAR-T target antigens, data from the Cancer Genomic Atlas were analyzed, comparing gene expression in oral tumors versus corresponding adjacent healthy tissues. To validate tumor antigen expression, three oral cancer cell lines (OQ01, HN, CAL27), an oral epithelial cell line (HOK) and 12 tumor specimens were analyzed by immunofluorescence. Oral tumor biopsies were stained with NTM antibody following antigen retrieval.
Results: NTM was overexpressed 6.4-fold in 303 oral cancer patient tissues versus healthy control tissues. All cell lines stained positively for NTM, with OQ01 demonstrating the strongest expression. NTM was localized mainly to the cytoplasm and cell surface, with heterogeneous patterns of expression between cell lines. Moreover, 11 out of 12 oral tumor biopsies were positively stained and one specimen clearly demonstrated cell surface expression of NTM.
Conclusions: NTM expression showed heterogeneity in cancer cell lines and tumor specimens, demonstrating that this protein is a potential target antigen for CAR-T immunotherapy for some oral cancer patients. NTM is a glycosylphosphatidylinositol (GPI)-anchored adhesion molecule forming surface complexes that influence neurite growth. GPI-anchored proteins have been described as biomarkers for several cancers, including overexpression in epithelial ovarian tumors. Further work is ongoing to determine whether NTM is a suitable CAR-T target.