A new type of vaccination specifically stimulates the immune cells of a cancer patient against all the antigens of his own cancer cells. Some patients are in prolonged remission in a pilot study.
Immune system recruitment has become a major issue in the fight against cancer and is slowly replacing chemotherapy. A new type of cancer vaccine, a "personalized vaccine," is showing promising results in a first clinical trial at the Perelman School of Medicine in Pennsylvania.
The personalized vaccine is made from the patients' own immune cells, which are exposed in the laboratory to tumor cell fragments of cancer of the same patient, then reinjected to initiate a global immune response against the same cancer.
The trial, conducted in patients with advanced ovarian cancer, is a pilot test to determine the safety and feasibility of the process, but the efficacy is clear: about half of the vaccinated patients have anti-tumor T responses, and these "responders" tend to live much longer without tumor progression than those who do not respond. The study is published in Science Translational Medicine.
New generation of cancer vaccine
Most of the cancer vaccines developed to date have been designed to recognize and attack a single specific molecule, such as a cancer cell surface receptor, a molecule found in all patients with this type of tumor.
The approach of the research team is more ambitious. Each vaccine is essentially personalized for a single patient, using its own tumor that has a unique set of mutations and therefore a particular set of targets for the immune system. It is also a vaccine against whole tumors, intended to stimulate a non-immune response against a single target of a single tumor, but hundreds or thousands of targets of the cells of this same tumor.
"The idea is to elicit an immune response that will target the tumor very widely, hitting a variety of tumor markers, including some that would only be found on this particular tumor," said Janos Tanyi, assistant professor of obstetrics and gynecology at Penn Medicine.
An awareness of the cells educating the immune system
The vaccine exploits the natural immune education process of T cells against tumors, but enhances it to help overcome the highly sophisticated defenses of cancer.
Tanyi and his colleagues made each patient's vaccine by screening the patient's peripheral blood cells for the appropriate precursor cells and then growing them in the laboratory in an environment of dendritic cells and tumor fragments.
Dendritic cells are like T-cell educators, essential for developing an effective immune response of T-lymphocytes. These cells normally ingest infectious pathogens, tumor cells or any other substance considered "foreign", and exhibit fragments of this exogenous agent to T cells and other cells of the immune system, in order to trigger a specific immune response.
The researchers exposed the dendritic cells to specially prepared extracts of the patient's tumor. They activated the immune cells with gamma interferon to make them more active, and injected them into the lymph nodes of the patient to initiate a T-cell response.
100% survival in responders
The team tested this strategy on a total of 25 patients, each of whom received a dose of their own dendritic cells exposed to fragments of their own tumor every three weeks, in some cases for more than six months. Half of the patients who could be evaluated showed large increases in the number of T cells specifically reactive to tumor material, indicating a good response to vaccination.
"The 2-year overall survival rate of these responder patients is 100%, while the rate for non-responders was only 25%," said Tanyi.
One patient, a 46-year-old woman, started the trial with stage 4 ovarian cancer after five cycles of chemotherapy, a stage that usually has a very poor prognosis. She received a total of 28 doses of her personalized vaccine over a two-year period, after which she remained disease-free for five years.
A large-scale study in progress
The discovery in several of the responders of vaccine-induced T cells that have a strong affinity for unique structures on the surface of their tumor ("neoepitopes") is also promising. In principle, an attack of tumors by such T cells should be particularly potent as well as highly tumor specific and would preserve healthy cells.
Tumors usually have a repertoire of molecular defenses that they can use to suppress or escape immune attacks, which is why cancer vaccines and immunotherapies have had mixed results in clinical trials to date. In the future, Tanyi and his colleagues hope to improve the effectiveness of their vaccine by combining it with other drugs that deactivate anti-tumor immune defenses.
A larger scale study with this new personalized vaccine technique is planned.