Friday, June 22, 2018

CAR T-Cell Therapy: Fifth Pillar of Cancer treatment

World Hematology 2018 is here again today with an information which is an emerging trend in the field of Cancer treatment today. So, here we go…..
For years, when we come to know that someone has Cancer, the first and the foremost thing every one of us tell, even before the Doctor tells, when it comes to treatment part is Surgery, Chemotherapy, Radiation therapy, Targeted therapy, Medicines, etc and when it comes to the side effects, we tell hair loss, fatigue, anemia, etc. But we have research going on in the  field and currently we hear about a new term called the CAR- T Cell therapy when we talk about Cancer. So, lets look at what it is? today.
CAR T-Cell Therapy is a type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so that they will attack the cancer cells. The T cells are actually taken from a patient’s blood and then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to it in the laboratory. This special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and are given to the patient by infusion.
In 2017, two CAR T-cell therapies were approved by the FDA, one for the treatment of children with acute lymphoblastic leukemia (ALL) and the other for the adults with advanced lymphomas. Many in the Cancer Community now call immunotherapy as the fifth pillar of Cancer treatment. A rapidly emerging immunotherapy approach is called adoptive cell transfer (ACT): collecting and using patients’ own immune cells to treat their cancer. There are several types of ACT (“ACT: TILs, TCRs, and CARs”), the one that has advanced the furthest in clinical development is CAR T-cell therapy. Until recently, the use of CAR T-cell therapy has been restricted to small clinical trials, largely in patients with advanced blood cancers. But these treatments have nevertheless captured the attention of researchers and the public alike because of the remarkable responses they have produced in some patients—both children and adults—for whom all other treatments had stopped working. Nevertheless, researchers caution that, in many respects, it’s still early days for CAR T cells and other forms of ACT, including questions about whether they will ever be effective against solid tumors like breast and colorectal cancer.
The different forms of ACT “are still being developed,” said Steven Rosenberg, M.D., Ph.D., chief of the Surgery Branch in NCI’s Center for Cancer Research (CCR), an immunotherapy pioneer whose lab was the first to report successful cancer treatment with CAR T cells. CAR T cells are the equivalent of “giving patients a living drug,” explained Renier J. Brentjens, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center in New York, another early leader in the CAR T-cell field. The backbone of CAR T-cell therapy is T cells, which are often called the workhorses of the immune system because of their critical role in orchestrating the immune response and killing cells infected by pathogens. The therapy requires drawing blood from patients and separating out the T cells. Next, using a disarmed virus, the T cells are genetically engineered to produce receptors on their surface called chimeric antigen receptors, or CARs. These receptors are “synthetic molecules, they don’t exist naturally,” explained Carl June, M.D., of the University of Pennsylvania Abramson Cancer Center. These special receptors allow the T cells to recognize and attach to a specific protein, or antigen, on tumor cells. The CAR T cell therapies furthest along in development target an antigen found on B cells called CD19. Once the collected T cells have been engineered to express the antigen-specific CAR, they are “expanded” in the laboratory into the hundreds of millions. The final step is the infusion of the CAR T cells into the patient. If all goes as planned, the engineered cells further multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill cancer cells that harbor the antigen on their surfaces.
Like all cancer therapies, CAR T-cell therapy can cause sometimes fatal side effects. One of the most frequent is cytokine release syndrome (CRS). As part of their immune-related duties, T cells release cytokines, chemical messengers that help to stimulate and direct the immune response. In the case of CRS, there is a rapid and massive release of cytokines into the bloodstream, which can lead to dangerously high fevers and precipitous drops in blood pressure. In many patients, both children and adults, CRS can be managed with standard supportive therapies, including steroids as researchers have gained more experience with CAR T-cell therapy. CRS is considered an “on-target” effect of CAR T-cell therapy—that is, its presence demonstrates that active T cells are at work in the body. Another potential side effect of CAR T-cell therapy—an off-target effect—is a mass die off of B cells, known as B-cell aplasia. CD19 is also expressed on normal B cells, which are responsible for producing antibodies that kill pathogens. These normal B cells are also often killed by the infused CAR T cells. To compensate, many patients must receive immunoglobulin therapy, which provides them with the necessary antibodies to fight off infections. More recently, another serious and potentially fatal side effect, swelling in the brain, or cerebral edema has been seen in some of the larger trials being conducted to support potential FDA approval of CAR T-cell therapies for patients with advanced leukemias. However, the problem appears to be limited, with the leaders of other trials of CAR T-cell therapies reporting no instances of cerebral edema. Other so-called neurotoxicities—such as confusion or seizure-like activity—have been seen in most CAR T-cell therapy trials. But in nearly all patients the problem is short lived and reversible, Dr. Brentjens said. There was speculation early on that these neurotoxicities might be related to CRS. But although researchers are still trying to get their hands around the mechanisms, he added, “I think most investigators [in the field] would agree that they’re distinct from CRS.”
Research on CAR T cells is continuing at a swift pace, mostly in patients with blood cancers, but also in patients with solid tumors.


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