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Updated: Aug 4, 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 28, 2010
L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient
Hao Hong1, Christine E Brown1, Julie R Ostberg1
1Department of Cancer Immunotherapeutics & Tumor Immunology and Hematology & Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, United States of America.
Abstract:
New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR)-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM) were then genetically modified to express an anti-L1-CAM CAR (CE7R), which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p.) administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.
Insights
New ovarian cancer immunotherapies show promise. Genetically engineered T cells targeting L1-CAM effectively reduced tumors and improved survival in preclinical models, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Ovarian cancer remains a leading cause of gynecologic cancer mortality, necessitating novel therapeutic approaches.
- Chimeric antigen receptor (CAR)-T cell therapy has shown success in hematological cancers, with emerging potential for solid tumors.
Purpose of the Study:
- To investigate the potential of L1-cell adhesion molecule (L1-CAM)-specific CAR-T cells as an immunotherapy for ovarian cancer.
- To evaluate the expression of L1-CAM in ovarian cancer and the efficacy of genetically modified T cells targeting this antigen.
Main Methods:
- Assessed L1-CAM expression on ovarian cancer cell lines, primary tumors, and ascites cells.
- Genetically engineered human central memory T cells (TCM) to express a CAR targeting the CE7 epitope of L1-CAM (CE7R+ T cells).
- Evaluated in vitro effector functions (cytokine secretion, cytotoxicity) and in vivo efficacy in an ovarian cancer xenograft mouse model.
Main Results:
- L1-CAM was highly over-expressed across various ovarian cancer samples.
- CE7R+ T cells demonstrated specific targeting and effector functions against ovarian cancer cells in vitro.
- Intraperitoneal administration of CE7R+ TCM significantly reduced tumor burden, inhibited ascites, and improved survival in mice.
Conclusions:
- L1-CAM is a promising target for ovarian cancer immunotherapy.
- Adoptive transfer of L1-CAM-specific CAR-T cells (CE7R+ T cells) represents a potential novel immunotherapy strategy for advanced ovarian cancer.
