Using Genetic Engineering to Treat Cancer

Genetically modified CAR T cells produced remission in leukemia patients

/ Author:  / Reviewed by: Joseph V. Madia, MD Beth Bolt, RPh

(RxWiki News) Many leukemias can be treated successfully, but if the disease doesn’t respond, patients are left with few options. A new therapy may change all that.

Recently, researchers developed a new technique that used viruses to reprogram the patient’s own T cells (white blood cells that help the body fight diseases and harmful substances) to identify and kill leukemia cells.

This new therapy has shown success in adults and children with leukemia. Several clinical trials have been conducted using this new therapy.

These researchers concluded that the T cells multiplied, mounted a strong response against the leukemia cells and continued to live in the body for over a year.

"Ask your oncologist about new therapies."

Research teams led by Stephan A. Grupp, MD, PhD from the Division of Oncology at Children's Hospital of Philadelphia and the Abramson Cancer Center at the University of Pennsylvania Perelman School of Medicine in Philadelphia, PA and Michael Kalos, PhD, from the University of Pennsylvania School of Medicine in Philadelpia, PA, conducted these studies.

People with leukemia who do not respond to standard treatment have limited treatment options. Dr. Grupp and his team developed a technique whereby he took a patient’s own white blood cells, called T cells, and used a virus to reprogram the cells to recognize and target tumor cells.  These modified cells were infused back into the patient where they hunted down and killed the leukemia cells. The genetically re-engineered cells are called CAR T cells, and the therapy is called CTL019.

In one study, the researchers gave this therapy to 16 children and four adults with acute lymphocytic leukemia (ALL) who had not responded to other treatments.

In that study, 14 patients (89 percent) had a complete remission of their disease, three patients did not respond to the treatment and three are still being evaluated.

A total of 11 of the patients were still in remission when followed up an average of 2.6 months later, and some patients still had remission 15 months later.  Three patients who had had a complete response relapsed. One of these patients was found not to have the target on their cells that the therapy was directed against.

One child treated with this CTL019 therapy was still in remission 20 months later.

The researchers reported that 59 patients have been treated with this therapy so far. In two different studies, 24 adults with chronic lymphocytic leukemia (CLL) were treated with the modified T cell therapy. Five patients had an incomplete remission response, seven had a partial response and 12 had no response within three months.

Right after getting the infusion of re-programmed cells, patients had reactions ranging from high fever, muscle pain, nausea, trouble breathing and low blood pressure. The research team recognized this as a result of the body reacting to the presence of the modified T cells and the cells multiplying and killing large amounts of leukemia cells. A medication called tocilizumab (brand name Actemra) along with corticosteroids helped to calm this response.

The researchers stated that it was important to note that this therapy did not cause graft-versus-host disease. This is a common side effect in which cells or organs put into the body fight the body itself. The reaction can have very serious consequences and be difficult to treat.

"Traditionally, cancer treatment has used toxins to kill cancer cells, which can affect the whole body causing side effects. This study shows a concept which changes the paradigm, where the treatment tweaks a patient’s immune system to fight off the cancer," said Subhakar "Sub" Mutyala, MD, Associate Director of the Baylor Scott & White Cancer Institute and Associate Professor at Texas A&M College of Medicine in Temple, Texas.

"This treatment, although early in study, could benefit patients with blood borne cancers such as leukemia, and potentially other malignancies," Dr. Mutyala told dailyRx News.

The researchers are conducting more studies to test how many new engineered cells should be put back into the patient. So far, no differences were seen using different numbers of cells on either response to the therapy or on rates of bad reactions.

Abstracts on this research were presented in December at the American Society of Hematology's Annual Meeting and Exposition in New Orleans.

Review Date: 
December 13, 2013
Last Updated:
February 19, 2014