The race to find the cure for cancer consists of a multibillion-dollar global research industry that has, in recent years, developed some promising therapies with the potential to change modern medicine as we know it. Treatments such as hyperthermia therapy, radio wave therapy, radiation therapy, immunotherapeutic vaccines, and Dichloroacetate (DCA) have all shown positive results in clinical and pre-clinical trials. However, one specific form of gene therapy is now proving to be amongst the most encouraging development so far, with ground-breaking results released this year. CAR-T therapy is a form of gene therapy treatment that has been dubbed the ‘living drug’ by researchers, and works by filtering a patient’s blood for key immune system cells and then genetically engineering these cells to recognize and fight cancer cells in the body.
A study released by Kite Pharma earlier this year involved 101 patients with Non-Hodgkin Lymphoma and found that by 6 months, 41% of patients had cancer that was responding to the treatment and 36% were in complete remission. Throughout the trial, 8 in 10 patients witnessed their cancer shrink by at least half. Senior Vice President of Clinical Development from Kite, Jeff Wiezorek M.D. has stated that there are clinical trial investigators who believe in the potential of CAR-T therapy to “change the paradigm of cancer treatment” and the results of this trial strongly indicate this as a possibility. As treatment currently stands, patients with aggressive lymphoma that has failed to respond to a previous treatment only see an 8% chance of achieving complete remission with current therapies but the results of this study suggest that CAR-T therapy may well become the standard of care for patients with refractory aggressive lymphoma.
CAR-T therapy was originally developed in the 1980s and uses T cells (a type of immune cell from the patient’s own blood) and genetically engineers these cells to produce special receptors on the surface called chimeric antigen receptors (CARs); these CARs then allow the T cell to recognize a specific antigen on cancer cells. These engineered T cells are then grown in the laboratory to create an army of billions that is then infused back into the patient. Assuming that all goes correctly, these genetically engineered T cells are then able to recognize and attack the cancer cells that harbor the antigen on their surface. Crystal Mackall, M.D. of the National Cancer Institute’s Pediatric Oncology Branch states that these CAR-T cells are “much more potent than anything we can achieve” with alternative immune-based treatments.
While this trial from Kite Pharma is the first large-scale clinical study, the National Cancer Institute has run smaller-scale studies in the past demonstrating equally promising results, including one trial with 20 children suffering from acute lymphoblastic leukaemia (ALL), which successfully led to a complete response from 14 of the children, 10 of whom have remained entirely cancer-free following a stem cell transplant.
However, these rewards from CAR-T therapy do not come without their risks. In one 2016 trial from Juno Therapeutics, 5 of 68 patients died during the trial and researchers were forced to suspend the study; in addition to this, deaths were also seen at the Memorial Sloan Kettering Cancer Center in 2014 as a result of a CAR-T therapy trial. Two patient deaths during the Kite Pharma trial were attributed to be the direct cause of the therapy. Side effects are severe, with the Kite Pharma trial recording that 43% of patients developed anemia, 39% developed neutropenia, 32% suffered a decreased neutrophil count, and 21% experienced encephalopathy. Perhaps the most worrying side-effect of CAR-T therapy is cytokine-release syndrome, which causes dangerously high fevers and devastating drops in blood pressure as a result of the rapid and massive release of cytokines into the bloodstream (cytokines are released by T cells and help carry out their duties). Within the Kite Pharma trial, 13% of patients experienced this syndrome but despite these results, Dr Steven Rosenberg of the National Cancer Institute maintains, “It’s a safe treatment, certainly a lot safer than having progressive lymphoma”.
The full data from Kite Pharma’s trial will be presented at the American Association for Cancer Research conference held in April of this year and as for patient access to CAR-T therapy, the company plans on submission for a license application within months as well as a marketing authorization application. CAR-T therapy is looking set to change cancer treatment as we know it – and soon.