Specific Ovarian Cancer-tailored Immunotherapy Appears Effective in Mouse Models

Specific Ovarian Cancer-tailored Immunotherapy Appears Effective in Mouse Models

Directing cancer immunotherapy against a specific protein on the surface of ovarian cancer cells may prove to be a tumor-specific approach to killing malignant cells while leaving healthy cells intact.

In the study “Follicle stimulating hormone receptor is expressed by most ovarian cancer subtypes and is a safe and effective immunotherapeutic target,” published in the scientific journal Clinical Cancer ResearchWistar Institute researchers analyzed human ovarian samples from 77 people with ovarian cancer and 20 healthy volunteers, discovering that a protein named follicle stimulating hormone receptor (FSHR) is expressed on the surface of different types of ovarian tumors but not on healthy tissues of non-ovarian origin.

Specifically, FSHR was found in 33 percent of clear cell ovarian carcinoma, 67 percent of mucinous ovarian carcinomas, and 70 percent of endometrioid carcinomas.

“Finding a receptor expressed exclusively on ovarian cells allows us to utilize groundbreaking targeted T-cell technology to potentially eliminate cancerous cells in patients,” senior study author Dr. José R. Conejo-Garcia said in a press release.

This means that treatments targeting this receptor would only affect ovarian tissue and eliminate the cancerous cells without affecting other tissues.

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.

The team developed a modified version of the CAR technology, called chimeric endocrine receptor-expressing T-cells (CER-T), whereby 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 eliminate ovarian cancer tumors of human origin which were transplanted into immunocompromised mice. When the T-cells were injected into mice with normal immune systems which were also transplanted with ovarian cancer cells, no adverse events were observed. Importantly, after T-cell injection, mice did not present any evidence of distress, weight loss, damage in healthy tissues, or modifications in liver enzymes and glucose.

These results reveal that these T-cells are able to specifically recognize and eliminate tumor cells in vivo and constitute a safe and efficient immunotherapeutic option for ovarian cancer. The researchers hope this approach could be used as a treatment following surgery and chemotherapy to stop cancer recurrence.

“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,” said study author Dr. Alfredo Perales-Puchalt.