Personalized Tumor Vaccine Shows Promise in Advanced Ovarian Cancer
A new type of cancer vaccine has yielded promising results in an initial clinical trial conducted at the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center of the University of Pennsylvania. The personalized vaccine is made from a patient’s own immune cells, which are exposed in the laboratory to the contents of the patient’s tumor cells, and then injected into the patient to initiate a wider immune response.
The trial, conducted in patients with advanced ovarian cancer, was a pilot study aimed primarily at determining safety and feasibility, but there were clear signs that the treatment could be effective: About half of the vaccinated patients showed signs of antitumor T-cell responses, and those responders tended to live much longer without tumor progression than those who didn’t respond. One patient, after 2 years of vaccinations, was disease-free for another 5 years without further treatment. The study was published by Tanyi et al in Science Translational Medicine.
“This vaccine appears to be safe for patients and elicits a broad antitumor immunity—we think it warrants further testing in larger clinical trials,” said study lead author Janos L. Tanyi, MD, Assistant Professor of Obstetrics and Gynecology at Penn Medicine.
Creating the Vaccine
Most cancer vaccines developed to date have been designed to recognize and attack a specific known molecule—such as a cell-surface receptor—that is likely to be found on cancerous cells in any patient with that type of tumor. The approach taken by this team is more ambitious—each vaccine is essentially personalized for the individual patient, using the patient’s own tumor, which has a unique set of mutations and thus a unique presentation to the immune system. It is also a whole-tumor vaccine, meant to stimulate an immune response against not just one tumor-associated target, but hundreds or thousands of targets.
“The idea is to mobilize an immune response that will target the tumor very broadly, hitting a variety of markers including some that would be found only on that particular tumor,” Dr. Tanyi said.
The vaccine harnesses the natural process of T-cell immunity to tumors, but enhances it to help overcome the considerable defenses of tumors. Dr. Tanyi and colleagues made each patient’s vaccine by sifting through the patient’s own peripheral blood mononuclear cells for suitable precursor cells and then growing these, in the lab, into a large population of dendritic cells.
Dendritic cells are essential for an effective T-cell immune response. They normally ingest infectious pathogens, tumor cells, or anything else considered foreign and redisplay pieces of the invader to T cells and other elements of the immune system to trigger a specific response. The researchers exposed the dendritic cells to specially prepared extracts of the patient’s tumor, activated the cells with interferon gamma, and injected them into the patient’s lymph nodes, in order to prime a T-cell response.
Response to Vaccination
The team tested this strategy on a total of 25 patients, each of whom received a dose of tumor-exposed dendritic cells every 3 weeks—in some cases, for more than 6 months. Half of the patients who could be evaluated showed large increases in the numbers of T cells specifically reactive to tumor material, indicating a good response to vaccination.
“The 2-year overall survival rate of these responder patients was 100%, whereas the rate for nonresponders was just 25%,” Dr. Tanyi said.
One patient, a 46-year old woman, started the trial with stage IV ovarian cancer—which generally has a very poor prognosis—following five prior courses of chemotherapy. She received 28 doses of her personalized vaccine over a 2-year period, and thereafter remained disease-free for 5 years.
Also promising was the finding, in tests on several of the responders, of vaccine-induced T cells that showed a high affinity for unique structures (ie, neoepitopes) on their tumors. In principle, an attack by such T cells on tumors should be particularly powerful, as well as highly tumor-specific, and thus sparing of healthy cells.
Dr. Tanyi and colleagues therefore hope in future to enhance the effectiveness of their vaccine by combining it with other drugs that deactivate tumor anti-immune defenses.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
