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Updated: Aug 15, 2026
An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 29, 2010
An antibody-tumor model for the targeting of CA125-producing gynecologic malignancies
1Department of Nuclear Medicine, Kyoto University School of Medicine.
Abstract:
By immunizing a mouse with HOUA-1 cells established from an endometrial cancer patient, two murine monoclonal antibodies designated 196-14 and 196-28 were generated, which were reactive with ovarian cancer-associated antigen CA125, originally defined by OC125 antibody. Antigenic determinants of these antibodies, although overlapping each other, were different from that of OC125 and the combined use of 125I-labeled 196-14 and OC125-coated beads markedly increased the sensitivity of measuring CA125 antigen. Both radioiodinated and 111In-labeled 196-14 localized well in CA125-producing human ovarian cancer tissues OVA-5 xenografted in nude mice. The biodistribution of radioiodinated 196-14 was quite different from that of 111In-labeled 196-14. Radioiodine was cleared faster from the OVA-5 tumor, making a clear contrast to the prolonged retention of 111In the tumor. Initial tumor uptake of radioiodinated 196-14 was the same as that of 111In-labeled 196-14 but decreased thereafter, due to the dehalogenation of radioiodinated antibody in the tumor. This antibody-tumor model seems to be suitable for examining the usefulness of monoclonal antibody-conjugates in the diagnosis and therapy of CA125-producing endometrial or ovarian cancers.
Insights
New monoclonal antibodies, 196-14 and 196-28, target ovarian cancer antigen CA125. Their combined use with OC125 enhances CA125 detection sensitivity and shows potential for diagnosing and treating ovarian and endometrial cancers.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- CA125 is a key biomarker for ovarian cancer.
- Existing antibodies like OC125 have limitations in detection sensitivity.
- Development of novel antibodies is crucial for improved diagnostics and therapeutics.
Purpose of the Study:
- To generate and characterize new monoclonal antibodies against CA125.
- To evaluate the diagnostic potential of these antibodies, individually and in combination.
- To assess the in vivo behavior of radiolabeled antibodies for tumor imaging.
Main Methods:
- Immunization of mice with HOUA-1 cells to produce monoclonal antibodies (196-14, 196-28).
- Characterization of antibody reactivity with CA125 and comparison with OC125.
- Assessment of combined antibody use for enhanced CA125 antigen measurement sensitivity.
- In vivo studies using radiolabeled antibodies (125I and 111In) in human ovarian cancer xenografts (OVA-5) in nude mice.
Main Results:
- Two novel monoclonal antibodies, 196-14 and 196-28, reactive with CA125 were generated.
- These antibodies recognize distinct epitopes compared to OC125.
- Combined use of 125I-labeled 196-14 and OC125-coated beads significantly increased CA125 detection sensitivity.
- Both radioiodinated and 111In-labeled 196-14 showed good localization in CA125-producing tumors.
- Differential biodistribution was observed, with 111In showing prolonged tumor retention compared to 125I due to dehalogenation of radioiodinated antibody.
Conclusions:
- Novel monoclonal antibodies 196-14 and 196-28 offer improved targeting of CA125.
- The combination of these antibodies enhances CA125 detection sensitivity, aiding in early diagnosis.
- Radiolabeled 196-14 demonstrates potential for imaging CA125-expressing tumors, with 111In-labeling showing favorable retention.
- The developed antibody-tumor model is suitable for evaluating antibody-conjugates for diagnosis and therapy in ovarian and endometrial cancers.
