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Updated: Mar 17, 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
Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective
Alfredo Perales-Puchalt1, Nikolaos Svoronos1, Melanie R Rutkowski1
1Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania.
Purpose:
To define the safety and effectiveness of T cells redirected against follicle-stimulating hormone receptor (FSHR)-expressing ovarian cancer cells.
Experimental Design:
FSHR expression was determined by Western blotting, immunohistochemistry, and qPCR in 77 human ovarian cancer specimens from 6 different histologic subtypes and 20 human healthy tissues. The effectiveness of human T cells targeted with full-length FSH in vivo was determined against a panel of patient-derived xenografts. Safety and effectiveness were confirmed in immunocompetent tumor-bearing mice, using constructs targeting murine FSHR and syngeneic T cells.
Results:
FSHR is expressed in gynecologic malignancies of different histologic types but not in nonovarian healthy tissues. Accordingly, T cells expressing full-length FSHR-redirected chimeric receptors mediate significant therapeutic effects (including tumor rejection) against a panel of patient-derived tumors in vivo In immunocompetent mice growing syngeneic, orthotopic, and aggressive ovarian tumors, fully murine FSHR-targeted T cells also increased survival without any measurable toxicity. Notably, chimeric receptors enhanced the ability of endogenous tumor-reactive T cells to abrogate malignant progression upon adoptive transfer into naïve recipients subsequently challenged with the same tumor. Interestingly, FSHR-targeted T cells persisted as memory lymphocytes without noticeable PD-1-dependent exhaustion during end-stage disease, in the absence of tumor cell immunoediting. However, exosomes in advanced tumor ascites diverted the effector activity of this and other chimeric receptor-transduced T cells away from targeted tumor cells.
Conclusions:
T cells redirected against FSHR+ tumor cells with full-length FSH represent a promising therapeutic alternative against a broad range of ovarian malignancies, with negligible toxicity even in the presence of cognate targets in tumor-free ovaries. Clin Cancer Res; 23(2); 441-53. ©2016 AACR.
Insights
Engineered T cells targeting follicle-stimulating hormone receptor (FSHR) show promise for ovarian cancer treatment. These FSHR-targeted T cells demonstrated effectiveness and safety in preclinical models, offering a new therapeutic avenue.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Follicle-stimulating hormone receptor (FSHR) is expressed in various gynecologic malignancies.
- FSHR presents a potential target for ovarian cancer immunotherapy.
Purpose of the Study:
- To evaluate the safety and efficacy of T cells engineered to target FSHR-expressing ovarian cancer cells.
Main Methods:
- FSHR expression was analyzed in ovarian cancer tissues and healthy tissues using Western blotting, immunohistochemistry, and qPCR.
- The therapeutic potential of FSHR-targeted T cells was assessed in patient-derived xenografts and immunocompetent mouse models.
Main Results:
- FSHR is present in diverse ovarian cancer subtypes but not in healthy non-ovarian tissues.
- FSHR-targeted T cells induced significant tumor rejection and improved survival in preclinical models with no observable toxicity.
- Engineered T cells persisted as memory cells and enhanced endogenous anti-tumor immunity, though exosomes in ascites posed a challenge.
Conclusions:
- T cells redirected against FSHR-positive ovarian tumors offer a promising therapeutic strategy.
- This approach demonstrates broad applicability across ovarian malignancies with minimal toxicity, even with FSHR presence in healthy ovaries.
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