Directing T-cells against a protein expressed in a variety of ovarian tumor cells may represent a major breakthrough in the treatment of ovarian cancer patients, according to an animal study published in the journal Clinical Cancer Research.
The study “Follicle-stimulating hormone receptor is expressed by most ovarian cancer subtypes and is a safe and effective immunotherapeutic target,” developed by researchers at The Wistar Institute in Philadelphia, reveals that T-cells can be effectively modified to recognize and attack ovarian cancer cells without adverse events.
“We began this research almost four years ago with the goal of finding a safe and effective immunologic approach to the treatment of epithelial ovarian tumors,” said Dr. José R. Conejo-Garcia, professor and program leader of the Tumor Microenvironment and Metastasis Program at Wistar and lead author of the study, in a press release. “Finding a receptor expressed exclusively on ovarian cells allows us to utilize groundbreaking targeted T-cell technology to potentially eliminate cancerous cells in patients.”
The researchers found that the follicle-stimulation hormone receptor (FSHR) is expressed in large numbers of serous ovarian carcinomas. Specifically, FSHR was found in 33% of clear cell ovarian carcinoma, 67% of mucinous ovarian carcinomas, and 70% of endometrioid carcinomas. Although the protein is also expressed in healthy ovarian cells, it is not found in other heathy tissues which suggests that a targeted therapy would only affect the ovaries.
Usually, immunotherapies that direct T-cells to eliminate specific subsets of cells rely on the chimeric antigen receptor (CART) T-cell technology, in which the T-cells are engineered to express a CAR protein that recognizes a specific antigen expressed at the surface of the tumor cells. But, the technology had been limited to B-cell blood cancers, such as chronic lymphocytic leukemia.
In the new study, the team led by Conejo-Garcia developed a modified version of the CAR technology, called chimeric endocrine receptor-expressing T-cells (CER-T). With the technology, the T-cells are modified to express the FSH hormone that binds to FSHR — instead of the antibody fragment that is used for CAR T-cells.
The FSH-expressing T-cells were able to induce rejection of human ovarian cancer cells in immunocompromised animals. When the T-cells were injected into mice with normal immune systems and bearing ovarian cancer, no adverse events were observed. In fact, following T-cell injection, mice did not present any evidence of distress, weight loss, damage in healthy tissues, or modifications in liver enzymes and glucose.
“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 and the study’s first author. “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.”