In the latest foray into personalized medicine, scientists design tumor vaccines specific to each patient’s tumor. Although the technology is in its infancy and the trial is small-scale, the findings are incredibly promising.
Most of these efforts have focused on designing a vaccine that recognizes a generic target on a tumor.
This method ensured that the vaccine would be able to attack most tumors, but it also meant that it lacked specificity — every tumor is different.
Recently, researchers set out to design a vaccine that is much more patient-specific. They attempted to tailor a vaccine to specifically match the patient’s individual disease.
The research took place across a range of institutions, including the University of Pennsylvania in Philadelphia and the Lausanne Branch of the Ludwig Institute for Cancer Research in Switzerland.
The team concentrated on people with advanced ovarian cancer, a particularly difficult cancer to manage; treatment normally involves surgery followed by chemotherapy and, although there is often a good response initially, patients tend to relapse and become resistant to treatment.
Though the study only set out to determine whether such a personalized treatment was possible and safe, the results were positive and the authors believe that the technology has enormous potential.
Each tumor has its own set of mutations, making it unique. The vaccine designed by the team was a so-called whole-tumor vaccine. This means that rather than targeting just one region of the tumor, it attacks hundreds, or even thousands, of sites.
Lead study author Dr. Janos L. Tanyi explains, “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.”
Naturally, T cells mount an immune response against tumors, but this vaccine heightens their attack and helps them to overcome the cancer’s robust defenses. The team’s results were published this week in the journal Science Translational Medicine.
To create these vaccines, Dr. Tanyi and team pored over the immune cells present in the patients’ blood. They were on the lookout for precursor cells that they could extract and grow in the laboratory. From these, they developed a population of dendritic cells.
Dendritic cells are messengers, of sorts, in that they consume antigen material (in this case, parts of a tumor) and present it to T cells to spark a response.
The dendritic cells were taken from the patients’ blood and then introduced to extracts of their tumors and activated with interferon gamma, which is a chemical that is critical in the immune response. Finally, they were injected into the patients’ lymph nodes.
This procedure was carried out on 25 patients. Each participant received a dose of the carefully harvested dendritic cells every 3 weeks. Some participants continued this regimen for 2 years.
Approximately half of the patients who could be evaluated experienced a significant increase in the number of T cells reactive to the tumor material. These “responders” tended to survive longer with no tumor progression, when compared with non-responders.
“The 2-year overall survival rate of these responder patients was 100 percent, whereas the rate for non-responders was just 25 percent.”
Dr. Janos L. Tanyi
One participant — a 46-year-old — had already received five courses of chemotherapy for ovarian cancer before the pilot study began. At the start of the trial, her cancer was classed as stage 4. Ovarian cancer is notoriously difficult to treat, and at stage 4, the 5-year survival rate is just 17 percent.
In this study, the patient received 28 doses of personalized vaccine, spread over 24 months. She remained cancer-free for 5 years.
The results are impressive, given the type and severity of cancer being treated, but it is important to remember that this is a pilot study and much more research will be needed.
“This vaccine,” explains Dr. Tanyi, “appears to be safe for patients, and elicits a broad anti-tumor immunity — we think it warrants further testing in larger clinical trials.”
There is a great deal of ongoing research that is looking at the body’s immune response to cancer and how it might be enhanced. To date, though, these efforts have had mixed results because tumors have an impressive suite of defensive techniques.
Dr. Tanyi believes that this vaccine might be particularly successful if it is paired with other drugs that weaken the tumor’s ability to fight the immune system.