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As a pharmacist, Kathy James feels well informed about the importance of being screened regularly for cancer. Although the 55-year-old family had no history of cancer in her family, she never missed her usual mammogram and submitted to regular breast exams. She was therefore stunned when, during one of these self-exams in May 2017, she felt a marble lump in her left breast. A visit to the doctor confirmed him. "The radiologist came in with his hands in his pockets and looked down and said," It does not look good, "James said, and after a biopsy, James and her husband learned that She was suffering from metastatic breast cancer.It was their 26th wedding anniversary.
James immediately wanted both breasts surgically removed, which would significantly reduce the risk of cancer spreading. "I wanted to finish with all that," she says. "I was really determined to undergo double mastectomy."
If James had been diagnosed five years earlier, she would probably have undergone radical surgery, even if it would not have guaranteed that her cancer would not spread or return. An oncologist friend advised her not to have surgery and referred it to Dr. Brian Czerniecki of the Moffitt Cancer Center, who told him about a pioneering study that he was conducting in order to test a whole new way to fight breast cancer. chemotherapy, radiotherapy or surgery, but exploiting the power of one's own immune system. The study and dozens of other similar projects are potentially rewriting the manual on breast cancer treatment, offering patients unprecedented options for controlling their disease and possibly even curing it.
The immune system strengthens the body's defense and offensive against unwanted intrusions: bacteria, viruses and even cancer cells. However, cancer is a thorny issue. Malignant cells develop from normal cells that start to grow uncontrollably, and the immune system is specifically programmed to not attack the body's own cells.
But scientists have found ways to train the body to recognize and destroy tumor cells, making immune-based treatments the newest and most promising weapon against many types of cancer. The first of these immunotherapy drugs approved to treat cancer began in the James Allison labs of MD Anderson Cancer Center and Dr. Tasuku Honjo of Kyoto University in the 1990s. They independently discovered different ways in which the Immune system is prevented from attacking tumor cells, which has earned them the 2018 Nobel Prize in Physiology or Medicine. Their discovery led to a new class of drugs, called checkpoint inhibitors, that allow the immune system to see cancer cells as the thieves responsible for the disease and attack them, dramatically improving remission rates. In the last five years, the Food and Drug Administration (FDA) has approved a dozen new drugs and cancer treatments that exploit the immune system. "All cancer patients will probably receive [immunotherapy] in five years it will be healing for many of them, "says Allison.
Immunotherapy treatments are especially effective against lung cancer, skin cancer and blood cancers such as leukemia and lymphoma. But immune-based treatments have not been as effective, or as numerous, for the most common cancers: colon, prostate and especially the breast. Of the more than 600,000 people who died of cancer in the United States in the past year, the vast majority of them had this type of solid tumors. The problem, says Dr. Robert Vonderheide, director of the Abramson Cancer Center at the University of Pennsylvania, is that "most breast cancers fall into the category of" cold "immunologic tumors, which means that the tumor has the ability to exclude the immune system, system or hide completely.This type of cancer is not easy to treat with current immunotherapies. "
Dr. Steven Rosenberg, one of the pioneers of immunotherapy, in his laboratories at the National Cancer Institute
Jesse Dittmar – Redux
At least not yet. Building on the basics established by Allison and Honjo with checkpoint inhibitors, researchers are finding creative ways to boost the immune system so that he considers tumors like breast cancer to be targets. " "rather than" cold "in the same way that infectious viruses like measles or influenza viruses report an answer. They do this by learning from effective treatments for diseases such as tuberculosis and HIV, which combine therapies; against cancer, they combine immune treatments with more traditional treatments, such as chemotherapy, surgery or radiotherapy, to reinforce any existing immune response. While chemotherapy and radiation in their current form destroy immune cells and malignant cells, modified formulas may be enough to stimulate an inflammatory response that wakes up the immune system to allow it to see tumor cells. Breast cancer researchers are exploring ways to deploy immunotherapy drugs, such as checkpoint inhibitors, to trigger the strongest immune response against tumors.
James was intrigued by the idea of training his body to fight his cancer as a more sustainable solution than short-term cycles of chemotherapy or radiation therapy. "Since my cancer tends to recur and is aggressive, I can not just stop once my year of treatment is over," she says. "I needed to continue." And now, for patients like her, more creative ways to boost the immune system against cancer are starting to appear. Dr. Steven Rosenberg, Chief of Surgery at the National Cancer Institute, is studying the mutations that cause breast cancer, isolating the few immune cells that are trying to fight cancer cells, boosting their numbers in the lab and reinjecting them. in his patients. He is convinced that this strategy could become the model for translating the same success as immunotherapy in cancers of the blood, lungs and skin into cancers more common in the breast, prostate and colon.
There is a reason Doctors have focused their early efforts on immunotherapy on cancers such as melanoma and lungs. These diseases tend to emerge because cells accumulate many mutations, or errors in their DNA, that require them to start abnormal and uncontrollable growth. Normally, mutations make cancer difficult to treat because they allow it to find new ways to avoid the treatments that are started. But when it comes to making immunotherapies work, they are a definite advantage. In the 1980s, Rosenberg was among the first to notice that these mutations also attract the attention of the immune system and that some immune cells can begin to infiltrate tumors.
At the time, said Rosenberg, "no one knew that there was an immune response against human cancers". He decided to try to use it to his advantage and finally developed a way to isolate these anti-cancer immune cells, called T cells, from 195 people with melanoma, increasing their number and reintegrating them to patients. So far, 30% of them have completely responded to the therapy, which means that their existing cancer cells have disappeared and they have not seen any tumors reappear for nearly seven years since the treatment.
Encouraged by this demonstration of immunological strength, doctors have begun to explore ways to harness the immune system to treat other cancers. Leukemias and lymphomas, which are formed when blood cells become malignant, can not be treated surgically and tend to reproduce even after chemotherapy and radiation therapy. But they are particularly sensitive to a type of immune therapy that involves replacing a patient's malignant blood with a population of his T cells that are treated to attack a common cancer cell receptor. Up to 90% of people with certain types of leukemia whose cancer has reoccurred after repeated cycles of standard treatments are in remission after receiving this form of immunotherapy. Such success has led the FDA to approve the first immune cell-based treatment, called CAR T, for a type of leukemia and other blood cancers in 2017.
But solid cancers – which are much more common – have fewer mutations and the tissues they invade (such as breast) can not be replaced as are blood cells, making immunotherapy more difficult. Vonderheide found that of the 7,000 tumors listed in a national genetic database, breast cancers were in the lowest 25% of tumors in terms of the number of mutations they carried. Because of this, breast cancers are also part of the lower half of all cancers with regard to the immune responses generated by the body. "Breast cancer is notoriously protective of the immune system," he says.
Judy Perkins Stage IV Breast Cancer Declines After Experimental Immune Therapy
Scott McIntyre – The Washington Post / Getty Images
Rosenberg is now studying ways to release breast cancer from the possibilities of immunotherapy. Building on his early work on T cell responses to cancer, he developed an experimental treatment tailored to each patient 's cancer and first tested it on people with dementia. 39, cancer of the liver, colon and cervix. Judy Perkins, the first breast cancer patient in her study, had stage IV cancer that had re-appeared and had turned into lumps in the breast and liver, despite a dozen chemotherapies and hormonal treatments and even a mastectomy. Using growing knowledge of the role of genes in cancer in genes, Rosenberg conducted extensive genetic analysis of his tumor and revealed 62 major mutations responsible for the malignancy of Perkins cells. He then researched some valiant immune cells capable of recognizing and attacking four of these genetic aberrations and already fighting his cancer. He extracted these immune cells, cultured them in greater numbers in the laboratory and sent them back to Perkins via IV as an immune treatment against his breast cancer.
Having exhausted all of her treatment options, Perkins had said goodbye to her loved ones and was "waiting for the end," she says. But a month after receiving the single infusion of cells, she felt the tumor in her chest become "softer and smaller." In two months, the growth of the size of a tennis ball in his liver was gone and the tumor in his chest had also disappeared. Shriveled to nothing. Nearly three years later, doctors say that she is in a lasting regression. "I am totally delighted. It's great, "she says. But Perkins knows for the moment that she is an exception. Until now, only 14% of the 42 people treated by Rosenberg responded to the same treatment as Perkins. Rosenberg thinks this percentage will increase if he and others find better ways to identify both the mutations at the base of each patient's cancer and the target immune cell population. As science evolves, immunotherapy may affect not only people with breast cancer but also those with other solid tumors. "This could be basically a plan for treating any type of cancer," he says. "And I honestly think it's a good chance to work."
There are limits. The Rosenberg immunotherapy method is a long and costly treatment, and since it requires a personalized approach, it can not be mass-produced as a standard universal procedure for any patient. There must be other ways to mobilize an immune response – that is why Czerniecki is testing in James and other patients for "vaccines" likely to look for and destroy cancer cells before they "get ready." they do not become tumors again.
James's breast cancer is HER2-positive, named after the protein that dominates his cancer cells – a protein that initially attracts an immune response and then loses it over time. Czerniecki has created a vaccine that stimulates this response again. "We try to restore some of the immune responses that are knocked out or softened over time," he says.
It's useful, but not enough in the case of James. As the disease progresses, cancer cells actively protect themselves from the immune system by covering themselves with proteins that are abundant on nearby healthy cells. Targeting cancer cells can also kill normal cells. "With invasive tumors, we have to play with their environment, because it has become almost a wall of the immune system in which we have to penetrate," says Czerniecki.
Ironically, one way to do this is to seek the help of older breast cancer treatment methods. At Penn, Vonderheide is experimenting with ways to combine new immunotherapy drugs with conventional treatments such as chemotherapy and radiotherapy, in the hope that the synergistic effect will make tumors more visible. and more vulnerable to immune attacks. According to Allison, the Nobel laureate, the idea is to "turn radiation and chemotherapy into a sort of vaccine."
The solution is not to use standard cycles of chemotherapy or radiotherapy, but to refine the treatments so that they are perfectly adapted to the activation of an immune response. Too much chemotherapy or radiation suppresses the immune system, but a sufficient amount can serve as a stimulant to activate it. "It's almost as if chemotherapy can make the surface of cancer cells rougher and achieve the desired result. [proteins] published that attract the immune system, "says Dr. Peter Schmid, Clinical Director of the Breast Cancer Center at St. Bartholomew Cancer Center in London.
Schmid will announce at the end of October the results expected from a study combining a chemotherapy agent combined with a checkpoint inhibitor for the treatment of advanced triple negative breast cancer, an aggressive form of the disease, difficult to treat. Chemotherapy comes in the form of nanoparticles, which makes it more soluble and better equipped to slip inside cell membranes to activate an immune response. "Patients ask me every day," Why do I need chemotherapy? Will not that weaken my immune system? Schmid says, "We only understand that this can have a more subtle and positive effect on cancer immunity."
There is similar enthusiasm for the combination of shorter radiation programs and control inhibitors. This approach is even more promising as a means of targeting tumors that have spread to hard-to-reach tissues – a common problem with breast cancer. Researchers believe that this is due to the fact that the radiation emitted over a few days rather than the standard program of several weeks may be sufficient to trigger an immune response against a specific tumor, which must then attack the tumor cells in other parts from the body. In the case of breast cancer, researchers hope that this response will detect outgrowths that have spread beyond the breast and target them. According to Allison, this new way of thinking is "really disruptive, because we realize with chemo and radiotherapy that we do not need to kill all the tumor cells, but that we stimulate enough for the immune system to suppress them."
Studies such as the one James is involved in could also upset current thinking about how to address one of the stubborn challenges of breast cancer: recurrent tumors. If vaccines designed to wake up immune cells against cancer are effective, breast cancer patients could potentially be protected from the return of their cancer through periodic "booster" cancer injections. Their immune system would be essentially ready to search for and eliminate all the cancer cells before they can fuse into tumors.
James and Perkins hope that their participation will accelerate the steady-state immune-based treatments for future breast cancer patients. James has received six inoculations of her anti-cancer immune cells during the summer and is expected to receive three recalls from January. "I can not change the fact that I have breast cancer, but I can pay for it by participating in a clinical trial in the hope that my children and my grandchildren will receive the vaccine so that They do not have to be vaccinated. endure what I went through, "she says. Perkins just wants his miraculous case to become the routine rather than the exception. "The immune system has such potential and we are just beginning to open that door," she says. "I hope this door will open completely and that we will have more effective treatments. I would like to have company to become the guinea pig of India. "
This appears in the October 15, 2018 issue of TIME.
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