Modified CAR-T prevents ovarian cancer growth in mice

FSHR is expressed in 33% of ovarian clear cell carcinomas--Courtesy of Michael Bonert CC BY SA 3.0(Michael Bonert CC BY-SA 3.0)

Wistar Institute scientists have used a modified version of CAR-T to target ovarian tumors in a new approach that could reduce the likelihood of recurrent cancer.

The researchers focused on a surface receptor protein found on several types of ovarian tumor cells: follicle-stimulating hormone receptor, or FSHR. This protein does not occur in healthy nonovarian tissue, representing a specific target for ovarian cancer treatment, according to a statement. FSHR is present in 70% of endometrioid carcinomas, 67% of mucinous ovarian carcinomas and 33% of clear cell ovarian carcinomas. The latter two are the most aggressive forms of the cancer.

The team, led by José Conejo-Garcia, a professor and program leader of the Tumor Microenvironment and Metastasis Program at Wistar, created a modified version of CAR-T (chimeric antigen receptor T cells) called CER-T, or chimeric endocrine receptor-expressing T cells. Unlike CAR-T, which directs T cells by recognizing an antibody fragment expressed by tumors, CER-T sends T cells to FSHR-expressing ovarian cancer cells using the full sequence of the FSH hormone, the team said. CAR-T has been gaining steam over the past few years, but has shown success only in B-cell blood cancers, the statement said.

Using CER-T, the team prompted the rejection of human-derived tumors in immunodeficient mice, according to the statement. They also saw no adverse effects when using the treatment in mice with tumors of mouse origin: there were no signs of weight loss or distress, the therapy had no effect on healthy nonovarian tissues and levels of glucose and liver enzymes were not affected.

It’s important to note, however, that the protein FSHR is also expressed in noncancerous ovarian cells. While therapy will not affect nonovarian tissue, it will affect healthy ovarian cells.

“Ideally, we’d like to see this technology used after initial treatment with surgery and chemotherapy,” said Dr. Alfredo Perales-Puchalt, a postdoctoral fellow in the Conejo-Garcia lab, in the statement. “Recurrence remains a major concern in the treatment of ovarian cancer, and so we believe the method we studied could be used to rid the patient of residual disease and drastically reduce the chance of the cancer returning.”

Last year, Wistar published findings that suggested inhibiting the enzyme EZH2 could cause tumor regression in ovarian cancer patients. Meanwhile, a team at Massachusetts General Hospital is working on a gene therapy to combat recurrent ovarian cancer. Delivering the protein Mullerian inhibiting substance to mice curtailed the growth of ovarian cancer.

- read the statement
- here's the study abstract

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