Clinical Perspectives

Using Immunotherapy to Combat Gynecological Cancers

March 28, 2018

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Gynecologic cancers are usually difficult to diagnose and challenging to treat. Physicians and researchers at Moffitt Cancer Center are exploring ways to harness the body’s immune system to better fight these cancers.

“There’s a limit to how far we can advance the treatment of cancer with chemotherapy, but with immunotherapy there isn’t a limit,” Dr. Robert Wenham, chair of the Gynecologic Oncology Program at Moffitt, said. “Instead of drugs that target a specific defect that may not be present in every cancer cell, or nonspecifically targeting the DNA of only quickly-growing cancer cells, immunotherapies can unleash an army of immune cells to constantly seek out and destroy cancer cells.”

The Gynecologic Oncology Program is actively participating in immunotherapy trials involving checkpoint inhibitors, vaccine therapy and cellular therapy. Checkpoint inhibitors are drugs that reverse the cancer cells’ block on the patient’s T cells so they can recognize and attack tumors.

Ovarian Cancer Applications

Doctors and researchers at Moffitt are currently involved in investigator-initiated drug trials and vaccine trials to help fight ovarian cancer. Dr. Wenham is leading a phase II trial testing the combination of checkpoint inhibitor Pembrolizumab with chemotherapy drug Paclitaxel to find out if it improves the time patients have without their cancer growing.

Dr. Wenham is also leading a large multi-institutional randomized phase II trial for a vaccine against a common protein on ovarian cancer cells called Folate Receptor Alpha. The goal is to help a patient’s body recognize ovarian cancer and keep it from coming back by building immunity against the target protein that is rarely found in healthy adult tissues, but is common in ovarian cancer tissue.

Moreover, early human clinical trials are using patient T-cells that have been extracted and then engineered to recognize other specific cancer proteins.

Cervical Cancer Applications

Doctors at Moffitt are also trying to combine check point inhibitors with other methods to treat cancer. Dr. Wenham is working with radiation oncologist Dr. Kamran Ahmed on an investigator-initiated trial for cervical cancer patients with metastatic disease. The goal is to combine stimulating a patient’s immune system via checkpoint inhibitors with radiating the tumor.

Moffitt is also working on vaccine trials for patients with recurrent metastatic cervical cancer with a high risk of the disease after initial chemotherapy or radiation. It is called Advaxis and couples a HPV particle with a Listeria particle to enhance the immune response toward virally infected cancer cells.

Moffitt also put the first patient on an ongoing cellular therapy against cervical cancer using an enriched infusion of the patients own cancer cells that were found attacking the cancer cells within the patient’s tumor.

Endometrial Cancer Applications

Check point inhibitors can be used for cancers that have a genetic abnormality called mismatch repair (MMR) deficiency. This prevents cells from fixing mistakes that occur when DNA copies itself. Since about a third of endometrial tumors are MMR-deficient, checkpoint inhibitors may be an effective strategy.

Dr. Jeannie Chern and Dr. Hye Sook Chon are both leading trials testing checkpoint inhibitors in people with endometrial tumors to try and reactivate the immune system to kill the cancer.
Though immunotherapy for gynecological cancers is currently lagging behind immune-based treatments for other some other cancers, such as melanoma and lung cancer, Dr. Wenham is confident immunotherapy will play a big role moving forward.

“I am actually optimistic for the first time that we may see entire groups of cancer wiped out in my lifetime,” Dr. Wenham said.