The first car-t cell therapy drug was unanimously approved by FDA experts

Source: the breakthrough chimeric antigen receptor T cell therapy (car-t) of Novartis Co., Ltd on July 12, 2017 was approved by the unanimous vote (10-0) of the FDA advisory expert committee The vote marks a key milestone in this type of experimental treatment FDA is expected to make a final approval decision on October 3 Carl June, a scientist at the University of Pennsylvania who led the development of drugs in this field, said it could open a new chapter in immunotherapy - "a truly viable drug." Car-t, manufactured by Novartis, is used only in a small number of children and adolescents with leukemia who do not respond to standard treatment These patients usually have a serious prognosis, but in critical trials in nearly ten countries, 83% of them are in remission A year later, two-thirds of patients are still in remission Childhood leukemia is just the beginning of a field of intense interest in academia and industry Kit pharmaceuticals, based in Santa Monica, California, has applied to the FDA for approval to treat advanced non Hodgkin's lymphoma, followed by a similar application from Novartis Researchers are also exploring car-t cell therapy for multiple myeloma and chronic lymphocytic leukemia They are also addressing a more difficult challenge - for example, the use of therapies for solid tumors in the lungs or brain Car-t cell therapy involves extracting white blood cells called T cells from a patient's blood (the guardians of the immune system), freezing them and delivering them to Novartis' giant manufacturing facility in Morris Plains, New Jersey There, T cells are genetically modified with modified HIV fragments so that they can find and attack cancer cells The modified cells were frozen and transfused back into the patient Once it enters the human body, the number of T cells increases dramatically The excitement of doctors and researchers is clear "We're saving patients who we didn't know what to do to keep them alive three or four years ago," said Stephen Schuster, an oncologist at the University of Pennsylvania who led the study of Novartis lymphoma Novartis' Lymphoma Research and kit's trials have shown that treatment drugs can alleviate about one-third of adult patients with advanced disease, who have exhausted all treatment options However, with enthusiasm comes the pressing issues of safety, cost and complexity of treatment Novartis has yet to disclose the price of its treatment, but analysts predict a one-time infusion of between $300000 and $600000 Brad Loncar, whose investment fund focuses on immunotherapy, hopes that spending will not trigger a backlash "Car-t is not Epipen, it's really beyond the limits and cutting edge of science," he said Security concerns, however, are the biggest concerns around security The accelerated immune system has become an effective anticancer agent, but also a dangerous threat to patients There are many serious side effects, which cause people's worry about widespread use "Safe treatment of patients is at the heart of the launch," said Stephan grupp of Philadelphia children's hospital The problem of effectiveness will be solved by itself, but security needs a lot of attention " Grupp is director of the cancer immunotherapy program at the hospital that leads early pediatric research and Novartis global trials One of the most common side effects is cytokine release syndrome, which can cause high fever and anxiety symptoms In some cases, it may be too dangerous for patients to be in intensive care Another major concern is neurotoxicity, which can lead to temporary confusion or potentially fatal brain edema Juno therapeutics closed its car-t program after five patients died of brain edema Novartis officials said it did not have brain edema in its tests To ensure the safety of patients, Novartis did not plan a typical product promotion as wide and active as possible Instead, the company will designate 30 to 35 medical centers for treatment Many of them participated in clinical trials and received a lot of training from grupp and others Grupp said he and his staff learned about the side effects of car-t cell therapy and how to deal with them through their terrible experience with Emily Whitehead five years ago Emily's routine treatment for acute lymphoblastic leukemia has recurred twice and is in critical condition Grupp advises her parents to make Emily the first child to receive experimental treatment After treatment, Emily's temperature soared, her blood pressure plummeted, and eventually her hospital's ICU coma and ventilator lasted for two weeks When grupp was convinced that Emily might not survive another day, he got laboratory results that showed that the surge of IL-6 protein caused her immune system to constantly attack her body The doctor decided to give an immunosuppressive drug called topiramab She got better in a few hours The next day, she woke up on her seventh birthday Tests showed that her cancer had disappeared The history of car-t approval of car-t cell therapy will represent the second major immunotherapy development in less than a decade In 2011, the FDA approved the first of a class of new drugs called immune check point inhibitors Since then, five other drugs have been approved There is a big difference between the two therapies Checkpoint inhibitors are for solid tumors, such as advanced melanoma, lung cancer, and bladder cancer, while car-t cell therapy is for hematopathy Although checkpoint inhibitors are readily available and each patient takes the same drug, car-t cell therapy is tailored to the individual Many immunotherapists believe that when researchers find out how to combine the two methods, they will achieve the greatest progress in cancer For the University of Pennsylvania team, the story of car-t cells dates back decades, starting in Bethesda, Massachusetts, later known as the National Naval Medical Center, where June and a postdoctoral researcher named Bruce Levine worked on new HIV treatment research In the process, they came up with a way to strengthen T cells to make them stronger and more abundant The two partners moved to Philadelphia in 1999 for cancer research Two years later, June's wife died of ovarian cancer, which encouraged him to work harder in this area In the years that followed, researchers from all over the country made a series of fascinating discoveries about T cells Fast forward to 2010, Bill Ludwig became the first university of Pennsylvania patient to receive car-t cell therapy The other two received treatment shortly after One was still in remission, the other died of recurrence But after the three patients, researchers at the University of Pennsylvania ran out of money to get more treatment In order to increase people's interest in and access to funding for the treatment, they decided to publish their findings An article published in the New England Journal of Medicine (NEJM) in August 2011 triggered a storm and brought them new resources The success of pediatric trials and Emily's treatment opens the next spring Six months later, the University of Pennsylvania transferred its technology to Novartis in exchange for funding, including a new campus cell manufacturing facility FDA approval seems to be coming, and researchers have played an important role in the development and testing of treatments.