First cancer gene therapy CAR-T in the U.S: The spark for a bright future


On July 2017, Novartis scored probably the most impressive goal of the year when their leukemia treatment got approval from the U.S Food and Drug Administration (FDA). The therapy, called chimeric antigen receptor T-cells (CAR-T), was the very first gene therapy to enter the U.S market and is said to have “[opened] a new era for medicine,” according to The New York Times.

The treatment was first developed and tested by Dr. Carl June and his team at the University of Pennsylvania in 2011. Back then, three patients took part in the experiment, among whom two had complete remission and one saw significant improvement. They were all victims of lymphocytic leukemia that failed to respond to chemotherapy.

The bad news is, CAR-T is no easy-to-go and mass-produced therapy. The treatment is designed case by case, based on individual components. Doctors first have to take millions of T-cells out of the patient’s bloodstream and re-engineer them by inserting disabled H.I.V viruses. These viruses carry a mixture of DNAs that once added into T-cells, they turn them into warriors that can detect and destroy cancerous B-cells in patients with acute lymphocytic leukemia (ALL).

The battle between the two can be furious and devastating. Patients often undergo high fever, low blood pressure, shaking with chills – symptoms resulted from what is called a cytokine storm when the chemical cytokine is released out of cells in the immune system. The kidney and liver might suffer, too, having to dispose of an abnormal amount of dead cells. What’s more, since the re-engineered T-cells are programmed to kill all the B-cells in the body, the patient will need to frequently inject intravenous immune globulins in place of B-cells to protect the body from infections.

Yet the results far outweigh the side effects. Of 63 patients enrolled in the trial, 83% went into complete remission within three months. After a year, 64% had yet to see any relapse. Once almost dead William Ludwig, one of the three patients receiving the therapy in 2011, confessed that he felt alive again; he took up golf and traveled on his new RV with his wife and nephews. Emily Whitehead, a successful case in 2012 that led to Novartis’s twenty-million-dollar investment in the experiment, has returned to school and regained her childhood at the age of 6.

ALL, often found in children, adolescents and young adults between 15 and 39, was reported to affect 81,837 American in 2014, and it is estimated that there are 5,970 new cases in 2017, of which 3,350 are males and 2,620 are females. The number of deaths is approximately 1,440. It is the most common pediatric cancer, with a portion of 26% of all cancers and 78% of leukemias in patients younger than 15 years. In Asia, though there hasn’t been any precise evaluation, researchers claim that there should be at least 54,000 new cases of ALL each year.

Acute lymphocytic leukemia happens when a lymphocyte – a type of immature white blood cell that is formed in the bone marrow starts to grow out of control. Direct causes of the disease are still unknown, but certain risk factors including exposure to radiation and cancer-causing chemicals such as benzene have been pointed out. Feeling of dizziness, bruising easily and frequent bleeding can result from low blood counts, and swelling of the liver, spleen and lymph nodes may occur when cancer spreads.

Research has been done to devise and test new treatment options for ALL. Chemotherapy is constantly improved, yet unwanted complications such as secondary cancer and behavioral problems remain. In some cases, cancerous cells evolve to become resistant to the therapy. Another option is stem cell transplantation, which has shown promising results in early studies, but certain effects are to be determined.

Therefore, the approval of CAR-T therapy has undoubtedly marked a revolutionary point in the unending fight against cancer, namely leukemia. Hopes are raised, and more companies will jump into the field to compete for the next life-saving treatment. David Epstein, once CEO of Novartis pharmaceutical divisions, said that he expected the life cycle of gene therapy to be shorter than conventional drugs and that the second generation might emerge in just a few years.

“This is the beginning of something big,” said Dr. Gwen Nichols, the current chief medical officer of the Leukemia and Lymphoma Society. Novartis plans to apply CAR-T in 30 to 35 medical centers in the U.S where the staff are trained, before submitting for approval from the European Union later this year. Of course, further observations are to be made to determine the long-term effects of the treatment, and major changes need to be done to scale up the process. However, there has been a spark, and the future is bright.