Scientists have worked for many years to use the power of the immune system. New approaches make researchers optimistic about success.
Vinod Balachandran, an oncologist and surgeon at the Memorial Sloan Kettering Cancer Center, said: “This is a very exciting time for the cancer vaccine industry.” “We have made great strides in understanding how the immune system recognizes cancer. There are dozens of candidates for the cancer vaccine being studied by researchers around the world. ”
The immune system plays an important role in the fight against cancer. Many experts believe that cancer is constantly trying to develop in us, but the immune system suppresses them before they can be identified, a process known as immune control.
“Our bodies are constantly rejecting cancer,” says Jay Berzofsky, head of the vaccine department at the National Cancer Institute. “We need to identify and treat those who have cancer, those who evade immune control. Tumors do this by learning how to use the mechanisms that regulate the immune system. ”
The new methods include the development of preventive and therapeutic vaccines, the second of which is designed to separate tumor cells from normal cells and trigger an immune response against them. Researchers are also collecting a collection of immunotherapeutic drugs that can increase the effectiveness of vaccines.
“They look like normal cells”
Cancer cells originate from our own cells and resemble them; Thus, the immune system is more resistant to them, says Berzofsky, a senior researcher and head of the NCI’s Department of Molecular Immunogenetics and Vaccine Research. “They hide the differences, so they look like normal cells,” he says. “The idea of a cancer vaccine is to activate the immune system, to choose ways to differentiate cancer from normal cells, to recognize them as foreign and to reject them.”
Tomorrow’s cancer treatment will be individual
It is important to understand how cancer vaccines differ from prophylactic vaccines and how immunotherapy drugs differ from the two types of vaccines.
Most people are familiar with traditional vaccines that protect against influenza and childhood diseases such as measles, mumps and whooping cough. Two vaccines have been approved to prevent viral infections that increase the risk of cancer: human papillomavirus (cervical and vaginal cancer, anal cancer, penile cancer) and hepatitis B virus (liver cancer).
However, scientists are also developing prophylactic vaccines for people with malignant diseases such as colon polyps, hoping to prevent them from developing cancer.
Targeted for the immune system
Olivera Finn, a prominent professor of immunology at the University of Pittsburgh, and her colleagues were the first to identify a specific tumor antigen — a protein or other molecule found only in cancer cells, not normal cells. immune system. (The term “antigen” refers to a toxin or other foreign substance in the body that is capable of generating an immune response.)
The tumor-specific Finn antigen, MUC1, is present in several types of cancer, including colon, breast, prostate, lung, and pancreas. He and his team developed a MUC1-based vaccine in clinical trials in patients with colon polyps that showed a strong immune response, blocking the growth of new polyps and preventing existing ones from turning into cancer.
According to Finn, the vaccine reduced the recurrence rate of polyps in a clinical trial by 38 percent.
“We and other groups are trying to strengthen the immune system by focusing on malignant lesions,” Finn said, adding that his group is about to start testing the same vaccine. ductal carcinoma in situ – the early stage of cancer, limited to breast milk ducts and not yet invasive – to see if the vaccine can stop its spread.
Therapeutic vaccines, unlike prophylactic vaccines, treat people with cancer by attacking cancer cells or preventing them from recurring. They stimulate the immune system to find and destroy cancer cells that have antigens specific to the tumor that do not have healthy cells. The vaccine delivers certain molecules that act like these antigens to stimulate the immune system to form new “killer” T cells. The same cells that also target viruses.
Keith Knutson, a cancer vaccine researcher at the Mayo Clinic in Florida, said: “Therapeutic vaccines include substances that stimulate the production of new immune cells that can fight cancer. “We stimulate the production of antigen – a miniature part of a protein, a fragment – of T cells capable of attacking a tumor.”
(So far, there is only one therapeutic vaccine on the market, Sipuleucel-T, which was licensed for prostate cancer in 2010. It doesn’t bring much benefit – clinical trials have shown it increases its overall lifespan to four months – but that’s enough. let the pharmaceutical board approve it, says Berzofsky.)
In some cases, experimental therapeutic cancer vaccines have been individualized, that is, they have been developed for a single person from the tumor samples of that patient. The goal, known as neoantigen vaccines, is to achieve the same results as other therapeutic vaccines. Neoantigens are caused by mutations that only affect human cancer cells.
“Targeting neoantigens is really new,” said Patrick Ott, clinical director of the Melanoma Disease Center at the Dana-Farber Cancer Institute, which has tested them for melanoma and other cancers. For example, in a recent small study, four out of six vaccinated patients had no recurrence of the tumor after 25 months. The tumor in the other two patients was enlarged, but they were completely regressive after taking additional immunotherapy drugs.
“They had amazing responses,” Ott says. “Perhaps the vaccine is designed to work with their immune system.”
The German company BioNTech, which is partnering with Pfizer, is researching neo-antigen vaccines in patients with pancreatic cancer, one of the most dangerous cancers, and developing a successful coronavirus mRNA vaccine. They use the same mRNA technology to make individualized vaccines and have treated 19 patients with pancreatic cancer since 2019. Preliminary results showed that half of the patients had a strong immune response to the vaccine and lived longer than half. their immune systems did not respond.
Genetic experimentation is difficult to treat cancer
“The big advantage of neoantigen vaccines is that they can have a strong immune response because they are adapted to each tumor and seem foreign to the patient’s immune system,” says Berzofsky. “Also, advances in mRNA technology – the same technology that has given us effective covid-19 vaccines – mean that neoantigen vaccines can be made quickly, eliminating previous major barriers.”
Many cancers also have common antigens, so individualized vaccines are not always needed. HER2 is an example of a molecule found in about 25 percent of breast cancers. Berzofsky’s laboratory is testing vaccines against several cancers, including HER2.
“It’s a ‘driver’ antigen, so cancer can’t happen without it,” Berzofsky said. “He will tell the cell: divide and multiply, so it would be very effective to follow him with the vaccine.” Early clinical trials have been promising, he says. There is a drug called Herceptin to treat patients with HER2-positive breast cancer, but “the patient should return in a few weeks to get a drip,” says Berzofsky. “If we had a vaccine that caused the patient to make his own HER2 antibodies, he wouldn’t have to come back for the medicine.”
“It could be revolutionary”
Knutson and Amy Degnim, breast surgeons at the Mayo Clinic in Minnesota, also developed the HER2 vaccine and recently conducted a small clinical trial in 22 patients with invasive breast cancer. According to Degnim, the vaccine, which is based on four fragments of the HER2 protein, stimulated both antibodies and T cells in all patients. The vaccine was given in six doses, one month apart.
A little over two years later, only two patients had relapses: one had another tumor in the breast, the other had the same recurrence in the lymph nodes, “that patient did not complete the vaccination course,” and only four patients received it. ok, Degnim says.
They hope to study the same vaccine in patients with intestinal carcinoma and prevent its development.
They are developing another vaccine, which they hope will completely prevent breast cancer in women at high risk. But first, it is checked for safety reasons – only in women with breast cancer.
“Once we have safety surveys – they haven’t started yet – then we need to think carefully about who should be registered for effective surveys,” Degnim said. But if it works, “it could be really revolutionary,” he says.
One of the first cases when researchers began researching vaccines against cancer was that tumors often had a detrimental effect on the immune system and suppressed it. Immunotherapeutic drugs can counteract these effects by blocking the immune system, and it can do its job. For example, “checkpoint” drugs, which work by preventing tumors from sending an “off” signal to the immune system, thus enable T cells to function.
Joshua Brody, director of the Lymphoma Immunotherapy Program at the Mount Sinai Cancer Institute, says the drugs release the immune system in combination with the immunosuppressive properties of cancer. with checkpoint inhibitors.
According to Finn, the development of checkpoint inhibitors – our pioneers won the 2018 Nobel Prize in Physiology or Medicine – was a breakthrough for the study of a cancer vaccine.
“Therapeutic vaccines initially failed because they could not stimulate the immune system, so both were suppressed. [cancer] with treatment and tumors, ”he said. “The suspects understood how to avoid the immune system. But now we know how the immune system of a person with cancer is suppressed and what the immunosuppressive environment is like.
Researchers are also trying to combine vaccines with other agents, including cytokines is The substances are usually released by the immune system, but in this case are produced in the laboratory. Cytokines are injected to increase the effectiveness of the vaccine.
“These different applications work synergistically,” says Jeffrey Schlom, co-director of NCI’s Center for Immunology and Oncology.
Some cancer patients may skip treatment, as 2 studies have shown
Although research is gaining momentum, experts warn that the widespread use of cancer vaccines will continue for several more years. Nevertheless, they assume that their use will become standard practice.
“We’re setting the stage,” Finn says. “I believe that in the future the time will come when doctors will identify the risk of certain cancers and give vaccines to prevent them.”
Schlom agrees. “It’s happening when we’re talking: more trials, more progress,” he says. “I think the best in terms of immunotherapy is still ahead. It’s just a matter of time. We put our feet in the door and now we are opening the door. ”