Using gene therapy consisting of a single injection of a modified sexual development protein stopped the growth of chemotherapy-resistant tumors in mice with ovarian cancer.
This was the result of a new study by Harvard Medical School (HMS) researchers at Massachusetts General Hospital (MGH) in Boston, who report their findings in the Proceedings of the National Academy of Sciences.
The team hopes the findings will lead to treatments that improve the survival of patients with ovarian cancer that recurs after chemotherapy, which happens in the majority of cases and is invariably fatal.
Lead author Dr. David Pépin, of the MGH Pediatric Surgical Research Laboratories, says:
“Our findings are important because there are currently no therapeutic options for recurrent, chemoresistant ovarian cancer.”
The protein at the center of the proposed gene therapy is called Mullerian Inhibiting Substance (MIS) and is important for sexual development.
In male embryos, MIS prevents the Mullerian duct from developing, which otherwise would give rise to female reproductive organs.
First test of MIS gene therapy in mice with chemoresistant ovarian cancer
In their study, the team showed how a commonly used viral vector called AAV9 carrying a modified version of MIS suppressed the growth of chemotherapy-resistant ovarian tumors in mice.
The mice used in the study had tumors grown from cells grafted from tumors of patients with highly resistant recurrent ovarian cancer.
Dr. Pépin notes that theirs is a “proof-of-concept” study that shows gene therapies using the AAV9 vector can be used to deliver biologics to treat ovarian cancer.
It is also the first study to test the MIS gene therapy in a mouse model of chemotherapy-resistant ovarian cancer, he says, noting that:
“If further study confirms the susceptibility of chemoresistant tumors to this MIS gene therapy, the ability to inhibit tumor recurrence could significantly extend patient survival.”
While not all the tumors they tested were sensitive to the MIS treatment, the team also developed a noninvasive way of testing cancer cells to see whether they are likely to respond to the gene therapy.
Response to MIS gene therapy is not the same for all patients
The team tested the MIS gene therapy in a number of ways. For example, they showed giving mice an injection of the therapy 3 weeks before implanting them with ovarian cancer cells significantly inhibited tumor growth.
And in another experiment, they gave the MIS therapy to mice that already had tumors growing in them from implants of cancer cells taken from five different patients. They found the therapy significantly blocked further growth of tumors arising from cells of three of the five patients.
The therapy is likely to be suitable only for patients who express the MIS protein receptor. In an analysis of tumor samples from over 200 patients, the researchers found 88% expressed some level of the MIS receptor, with 65% expressing it at a moderate or high level. Dr. Pépin comments:
“Since the response to MIS gene therapy is not the same for all patients, it will be important to first screen each patient’s tumors to ensure they will respond.”
He says they are currently searching for suitable biomarkers of treatment response from which to develop a screening tool.
The study follows another Medical News Today learned about earlier this year of a biomarker that may improve ovarian cancer treatment.
The researchers behind that study suggest their discovery could lead to better selection of treatments for patients with high-grade serous ovarian cancer (HGSC).
Written by Catharine Paddock PhD