T Cells Can Target Receptor Found on Many Ovarian Tumors

A laboratory study found that follicle-stimulating hormone receptors (FSHRs) are expressed in many ovarian tumors, and not in normal ovarian tissue, and thus represents a promising therapeutic target. Using human T cells targeted at those FSHRs increased survival in mice and could represent a novel approach to treating ovarian cancer.

Five-year survival rates for ovarian cancer patients have barely changed over the past 40 years. “Ovarian cancer is, however, an immunogenic tumor,” wrote study authors led by José R. Conejo-Garcia, MD, PhD, of the Wistar Institute in Philadelphia.

The study first involved testing for FSHR expression in various ovarian tumor cell lines, and then tested whether modified T cells could target that receptor. The results were published in Clinical Cancer Research.

In an initial analysis of 404 high-grade serous ovarian carcinomas (which represents about 70% of all epithelial ovarian cancers), 56.4% of the tumors expressed FSHR mRNA. It is not expressed in other healthy tissue including liver, contrary to some other recent research.

A further analysis of 28 stage III/IV serous carcinomas from the Wistar Institute’s tumor bank showed that 50% expressed FSHRs. Other histologic subtypes were even more likely to express FSHRs: it was found in 70% of endometrioid carcinomas, 67% of mucinous carcinomas, and was less prominent in clear cell carcinomas at 33%. FSHRs were not found in ovarian carcinosarcomas.

The researchers then used a modified version of chimeric antigen receptor T-cell technology to target the receptor. These T cells were used to treat mice with ovarian malignancies.

The T cells “induced rejection” of a patient-derived xenograft that expressed the highest FSHR levels, and also delayed the growth of a tumor with lower FSHR levels than is found in most primary ovarian malignancies. The researchers noted that the antitumor effects of the treatment do seem to depend on FSHR expression levels.

In another mouse experiment, only two intraperitoneal injections of the chimeric T cells were sufficient to significantly prolong survival of mice with an “aggressive” ovarian tumor. Importantly, no obvious adverse effects were seen, including no evidence of weight loss or signs of distress.

“Overall, our study demonstrates the effectiveness and safety of targeting chimeric receptors for T-cell activation using full-length hormones and unveils mechanisms of therapeutic activity that contribute to understanding the effects of adoptively transferred T cells in ongoing and future clinical trials,” the authors concluded. In a press release, they suggested that in the future this therapy could possibly be used after initial surgery and chemotherapy as a way to reduce the chances of recurrence.