WASHINGTON – A novel ovarian cancer treatment that uses the patient’s own tumor to stimulate her immune system provoked a positive response in 66% of women with advanced stage disease – including 20 patients who had no obvious disease at the end of treatment, and one who is still in complete remission nearly 4 years later.
When researchers added a second step of T-cell reprogramming for patients with residual disease, clinical benefit was seen in about 75% of patients, Lana Kandalaft, Ph.D., said during a press briefing at the annual meeting of the American Association of Cancer Research.
"This is the first time such a combination immunotherapy approach has been used for patients with ovarian cancer," said Dr. Kandalaft of the University of Pennsylvania. "Most patients with ovarian cancer are diagnosed at an advanced stage and many of those relapse within 2 years; most die within 5 years. Given these grim outcomes, there is definitely a vast unmet need for the development of novel, alternate therapies."
The team reported on its first 6 patients in January (Oncoimmunology. 2013;2: e22664). Four patients achieved clinical benefits, defined as tumor shrinkage of at least 30%. Two had a partial response; one with a partial response had previously progressed on chemotherapy alone but improved after the vaccine was added to her treatment, suggesting that immunomodulation conferred an additional therapeutic benefit.
Two other subjects exhibited stable disease. One of these still in remission. The last two patients continued to progress.
At the press briefing, Dr. Kandalaft reported on 31 patients – the original cohort plus 25 more women. All had recurrent progressive stage III or IV ovarian cancer and had undergone surgical reduction with tumor cryopreservation. The immunotherapy regimen began after each patient completed chemotherapy.
At that point, Dr. Kandalaft and her colleagues prepared a tumor lysate and used it to prime harvested dendritic cells. Patients received this individualized vaccine through intranodal injections in the groin, along with bevacizumab and cyclophosphamide, every 2 weeks for 3 months.
Eleven patients who responded to the vaccine treatment but still had residual disease moved to a second step: 3 months of adoptive T-cell therapy. Dr. Kandalaft and her colleagues removed T-cells, which had been educated in the body by the tumor-stimulated dendritic cells, and expanded these in culture. They then transferred the T-cells back to the patient, creating a population completely primed to attack the tumor.
Of these 11 patients, seven showed stable disease and one had a complete response.
Dr. Kandalaft noted that there is set length for this treatment, because each patient’s vaccine amount is limited by her tumor’s size and characteristics. During the follow-up period, patients receive the treatment until their supply is exhausted. The woman who remains in remission has been without vaccine for about a year, Dr. Kandalaft noted.
The team continues to refine the protocol. Some patients are now taking aspirin in addition to bevacizumab and cyclophosphamide. "We have some evidence from the lab that aspirin opens the endothelial barrier on the tumor and makes it easier for the T cells to attack."
Side effects are common, but so far have been mild or moderate; most were flu-like symptoms as well as the adverse events usually associated with bevacizumab and cyclophosphamide.
The study continues to accrue patients, Dr. Kandalaft said. Although other facilities are not approved to administer the vaccine, women with recurrent stage III or IV ovarian cancer who meet the eligibility criteria can still participate.
"These women would have their surgery at their own facility, and have the tumor cryopreserved according to our specifications, and then sent to us," Dr. Kandalaft said. "Then we would prepare the lysate and the woman would come to us for the remainder of her treatment.
She hopes to include a new set of patients as well – those who are in early remission after their primary treatment. "The immune system is healthier in this setting," she said. "For these women we will be trying to boost that system to prevent a recurrence in the first place. We think that is population who would get the biggest benefit from this treatment."
The study was funded by a National Cancer Institute Ovarian Specialized Program of Research Excellence grant, the National Institutes of Health and the Ovarian Cancer Immunotherapy Initiative.