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Interaction of monoclonal antibodies with cell surface antigens of human ovarian carcinomas
Abstract:
Two monoclonal antibodies, OC 125 and OC 133, bind to distinct determinants on the surface of human epithelial ovarian carcinoma cell lines. OC 125 and OC 133 recognize determinants on molecules with molecular weights greater than 200,000 and 80,000, respectively. When binding to four different cell lines was compared, apparent affinity constants for OC 125 ranged from 3.1 X 10(9) to 6.0 X 10(7) M-1, whereas those for OC 133 ranged from 1.6 X 10(9) to 8.5 X 10(8) M-1. An estimate of the number of antigenic determinants per cell ranged from 1.0 X 10(7) to 2.8 X 10(5) for OC 125 and from 4.0 X 10(5) to 3.4 X 10(4) for OC 133. Antigenic determinants recognized by OC 125 and OC 133 could be detected in spent culture medium. When radiolabeled OC 125 was incubated with each of four ovarian tumor cell lines, approximately 90% of the antibody remained bound to the tumor cell surfaces for more than 20 hr. Similar binding of OC 133 was observed with three of the four ovarian tumor cell lines. By contrast, greater than 70% of OC 133 antibody was either shed or endocytosed after binding to OVCA 433 cells over the same period. Antigenic modulation was not induced by either antibody interacting with any of the four cell lines. These data suggest that antigen may be lost from the surface of human ovarian carcinoma cells by several different mechanisms and that antigen release is not inconsistent with binding of radiolabeled antibody to the tumor cell surface for prolonged periods.
Insights
Two monoclonal antibodies, OC 125 and OC 133, target distinct ovarian cancer cell surface antigens. Antigen release mechanisms vary, with some antibodies showing prolonged binding to tumor cells.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Monoclonal antibodies (mAbs) are crucial tools in cancer research and therapy.
- Understanding antibody-epitope interactions on cancer cells informs diagnostic and therapeutic strategies.
- Human epithelial ovarian carcinoma cell lines express surface antigens recognized by specific mAbs.
Purpose of the Study:
- To characterize the binding properties of two distinct monoclonal antibodies, OC 125 and OC 133.
- To investigate the molecular targets and affinity of these antibodies on ovarian cancer cells.
- To explore mechanisms of antigen release from ovarian carcinoma cell surfaces.
Main Methods:
- Utilized cell binding assays with human epithelial ovarian carcinoma cell lines.
- Determined apparent affinity constants and quantified antigenic determinants per cell.
- Assessed antibody binding stability and antigen shedding/endocytosis over time.
- Investigated antigenic modulation induced by antibody-antigen interactions.
Main Results:
- OC 125 and OC 133 bind to distinct surface molecules (>200,000 Da and >80,000 Da, respectively).
- Antibody affinities varied, with OC 125 showing higher affinity constants on average.
- Antigenic determinants were detectable in culture medium, indicating release mechanisms.
- OC 125 demonstrated prolonged binding (>20 hr) to tumor cells, while OC 133 showed variable binding stability, with significant shedding/endocytosis in one cell line.
- Neither antibody induced significant antigenic modulation.
Conclusions:
- Ovarian carcinoma cells release surface antigens through multiple mechanisms.
- Antibody binding stability is cell-line dependent and may involve shedding or endocytosis.
- These findings provide insights into the dynamic nature of tumor antigens and antibody interactions.