Immunotherapy triggers antitumor responses in advanced ovarian cancer
A two-step personalized immunotherapy therapy treatment, which involved a dendritic cell vaccine using the patient's own tumor followed by adoptive T-cell therapy, triggered antitumor immune responses in these patients. Four of the six patients treated in this trial responded to the therapy.
This study builds on research from 2003 by the study's senior author, George Coukos, MD, PhD, of Perelman School of Medicine at the University of Pennsylvania in Philadelphia, which showed that women whose ovarian tumors were infiltrated by healthy T cells, tended to live longer than women whose tumors were devoid of T cells. That observation led to investigators to find ways to use patients' own tumor cells to boost the immune system's power.
This current study treated six women with advanced ovarian cancer in a two-staged immunotherapy protocol that used a dendritic cell vaccine created from tissue in the patients' own tumor, which was stored at the time of surgery. All of these women's cancers had progressed on standard of care chemotherapy.
In the first segment of the study, individualized dendritic cell vaccines were prepared for each patient by harvesting dendritic cells using apheresis. Then each patient's dendritic cells were exposed to tumor extract produced from the woman's own tumor, teaching the dendritic cells who the enemy is. After this priming, the investigators vaccinated each patient with her own dendritic cells and gave them a combination chemotherapy regimen of bevacizumab and cyclophosphamide. Because dendritic cells are like the generals of the immune system, they then induce responses from other immune cells.
Of the six patients who received the dendritic cell vaccine, four developed an anti-tumor immune response, indicating that the approach was working. One of those patients had no measurable disease at study entry because all of it had been successfully removed during surgery. She remains in remission today, 42 months after vaccine treatment. The other three who had an immune response to the vaccine still had residual disease and went on to the second segment of treatment.
The team harvested T cells from each of these three women. Using a technique developed at University of Pennsylvania, they grew the cells in the laboratory, expanding their numbers exponentially, and then reintroduced them into each patient after she underwent a lympho-depleting chemotherapy regimen. Because the T cells had already been trained by the dendritic cell vaccine to attack the tumor cells, the adoptive T-cell transfer amplified the antitumor immune response.
Two of the women showed a restored immune response after the T cell transfer. One of the women continued to have stable disease, whereas the other had a complete response to the therapy.
The researchers say it is too early to say whether this type of therapy will be effective in a large number of patients with ovarian cancer, but the early results are promising. First, and foremost, the two-step approach appears safe and well tolerated by the patients. In addition, the team saw a correlation in both treatment steps between immune responses and clinical benefit, suggesting that the immune response is, in fact, holding the disease in check. This trial was reported in OncoImmunology (2013;2:1-9).