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Monoclonal antibody JSB-1 detects a highly conserved epitope on the P-glycoprotein associated with
R J Scheper1, J W Bulte, J G Brakkee
1Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Abstract:
Resistance to multiple chemotherapeutic agents is a common clinical problem in the treatment of cancer. This resistance may occur before primary therapy or be acquired during treatment. We have generated a monoclonal antibody (MAb) (JSB-I), specific for a conserved epitope on the plasma membrane 170- to 180-kDa glycoprotein, the expression of which is strongly correlated with the degree of multi-drug resistance (MDR). JSB-I strongly binds to both Chinese-hamster-derived MDR cell lines and human MDR cell lines, including cell lines derived from lung and ovary. A drug-sensitive revertant line, and the corresponding drug-sensitive parent lines, showed only weak reactivity or none at all. JSB-I reacts strongly to air-dried or acetone-fixed cells and therefore has potential value for diagnostic detection of MDR cells in human tumor samples.
Insights
A new monoclonal antibody, JSB-I, targets a glycoprotein linked to multi-drug resistance (MDR) in cancer. This antibody shows potential for diagnosing MDR in patient tumor samples.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Chemotherapeutic resistance is a significant challenge in cancer treatment, either pre-existing or acquired.
- Multi-drug resistance (MDR) impacts treatment efficacy across various cancer types.
- Identifying reliable biomarkers for MDR is crucial for effective cancer therapy.
Purpose of the Study:
- To develop a diagnostic tool for detecting multi-drug resistance (MDR) in cancer cells.
- To characterize a novel monoclonal antibody (MAb) targeting a specific glycoprotein associated with MDR.
Main Methods:
- Generation of a monoclonal antibody (MAb) designated JSB-I.
- Characterization of JSB-I specificity for a 170- to 180-kDa plasma membrane glycoprotein.
- Testing JSB-I reactivity against drug-resistant and drug-sensitive cell lines (Chinese hamster and human origin).
Main Results:
- JSB-I specifically binds to a glycoprotein strongly correlated with the degree of multi-drug resistance (MDR).
- The antibody demonstrated strong binding to both Chinese hamster and human MDR cell lines, including lung and ovarian cancer lines.
- Drug-sensitive cell lines exhibited minimal or no reactivity with JSB-I.
- JSB-I showed robust reactivity with fixed cells, indicating suitability for diagnostic applications.
Conclusions:
- The monoclonal antibody JSB-I is a specific marker for a glycoprotein associated with multi-drug resistance (MDR).
- JSB-I has significant potential for the diagnostic detection of MDR cancer cells in clinical tumor samples.