Generation and Characterization of Monoclonal Antibodies Against Oral Cancer
Date Issued
2004
Date
2004
Author(s)
Chen, Yi-Fang
DOI
en-US
Abstract
Oral cancer accounts for two to four percent of all cancers diagnosed annually in the United States, but relative survival rates are among the lowest of major cancers. Only one-half the number of persons diagnosed with oral cancer are alive five years after the diagnosis. Treatment of epidermal malignancies, including oral cancer, has been largely based on chemotherapy and radiotherapy. Although improvement in response rates and survival has been obtained with these therapies over the years, a significant proportion of patients do not response or relapse. Moreover, conventional cytotoxic therapy is often associated with significant morbidity.
Over the last years, monoclonal antibodies (MAbs) have repeatedly made the successful transition from the bench to the bedside by the US Food and Drug Adminstration (FDA) for use in various clinical settings, including cancer therapy. In this study, we report the generation and characterization of two MAbs, OC23-38 and OC44-18, against oral cancer cells, SAS. The hybridoma-producing MAbs to SAS were selected following enzyme-linked immunosorbent assay (ELISA)-based screening, obtained from a fusion of immunized mouse splenocytes with NS1 myeloma cells. The specificity of these antibodies was further confirmed by the immunofluorescence, Western blot and flow cytometric assays. In Western blot analysis, OC23-38 and OC44-18 recognized SAS antigens with a signal discrete band about 66 and 52 kDa, respectively. Flow cytometric analysis performed using oral cancer cell, other cancer cells and normal human cells revealed that these MAbs exhibited high binding affinity with oral, NPC, prostate, ovary, colon, and lung cancer cells, but did not with normal cells. The B-cell epitopes of these two MAbs were further identified by phage display method. Furthermore, in TUNEL and MTT assays, the MAb OC23-38 can even inhibit SAS cells to proliferate and induce apoptosis. Finally, in the animal experiment, the treatment of tumor-bearing mice with this functional MAb OC23-38 also suppressed tumor growth in vivo. The data suggest that these MAbs, OC23-38 and OC44-18, might be useful to identify tumor-associated antigens and developed ligand-targeted therapy in the treatment of oral cancer.
Subjects
單株抗體
口腔癌
oral cancer
monoclonal antibody
SDGs
Type
other
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