A new type of vaccination makes it possible to specifically stimulate the immune cells of a cancer patient against all the antigens of the cells of his own cancer. Some patients are in prolonged remission in a pilot study.
Recruitment of the immune system has become a major issue in the fight against cancer and is gradually replacing chemotherapy. A new type of cancer vaccine, a “personalized vaccine,” shows promising results in an initial clinical trial at the Perelman School of Medicine, Pennsylvania.
The personalized vaccine is made from patients’ own immune cells, which are exposed in the laboratory to fragments of cancer tumor cells from the same patient, and then reinjected to initiate an overall immune response against the same cancer.
The trial, conducted in patients with advanced ovarian cancer, is a pilot trial to determine the safety and feasibility of the process, but the effectiveness is evident: about half of 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 receptor on the surface of the cancer cell, a molecule found in all patients with this type of tumor.
The research team’s approach is more ambitious. Each vaccine is essentially personalized for a single patient, using their own tumor which 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 an immune response not against a single target of a single tumor, but hundreds or thousands of targets of cells of the same tumor.
“The idea is to elicit an immune response that will target the tumor very broadly, hitting a variety of tumor markers, including some that would only be found on that particular tumor,” said Janos Tanyi, assistant professor of obstetrics. and gynecology at Penn Medicine.
Sensitization of the educating cells of the immune system
The vaccine harnesses the natural process of T cell immune education against tumors, but enhances it to help overcome the highly sophisticated defenses of cancers.
Tanyi and his colleagues made each patient’s vaccine by screening the patient’s peripheral blood cells for the appropriate precursor cells, then growing them in the lab, in an environment of dendritic cells and tumor fragments.
Dendritic cells are sort of educator cells for T lymphocytes, essential for developing an effective immune response from T lymphocytes. These cells normally ingest infectious pathogens, tumor cells or any other substance considered to be “foreign”, and exhibit symptoms. fragments of this agent exogenous to T lymphocytes and other cells of the immune system, in order to trigger a specific immune response.
The researchers therefore exposed the dendritic cells to specially prepared extracts from the patient’s tumor. They activated the immune cells with gamma interferon to make them more active, and injected them into the patient’s lymph nodes, in order to initiate a T-cell response.
100% survival among 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 strong increases in the number of T lymphocytes specifically reactive to tumor material, indicating a good response to vaccination.
“The 2-year overall survival rate for these responder patients is 100%, while the rate for non-responders was only 25%,” Tanyi said.
One patient, a 46-year-old female, 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, and thereafter remained disease-free for five years.
Researchers created a personalized vaccine that is safe and effective for the treatment of advanced ovarian cancer @PennMedicine @unil https://t.co/VefZ6zztSU pic.twitter.com/zhWXzhTNni
– Science Translational Medicine (@ScienceTM) April 13, 2018
A large-scale study underway
The discovery in several of the responders of vaccine-induced T lymphocytes which have a strong affinity for unique structures on the surface of their tumor (“neoepitopes”) is also promising. In principle, attack on tumors by such T lymphocytes should be particularly potent as well as highly tumor specific and would preserve healthy cells.
Tumors typically have a repertoire of molecular defenses that they can use to suppress or evade immune attacks, which is why cancer vaccines and immunotherapies have had mixed results in clinical trials to date. Tanyi and his colleagues therefore hope in the future to improve the effectiveness of their vaccine by combining it with other drugs that deactivate the anti-tumor immune defenses.
A larger scale study with this new personalized vaccine technique is planned.
.
