Leukemia patients remain in remission more than two years after engineered T cell therapy

December 10, 2012

Nine of twelve leukemia patients who received infusions of their own T cells after the cells had been genetically engineered to attack the patients' tumors responded to the therapy, which was pioneered by scientists in the Perelman School of Medicine at the University of Pennsylvania. Penn Medicine researchers will present the latest results of the trial today at the American Society of Hematology's Annual Meeting and Exposition.

The clinical trial participants, all of whom had advanced cancers, included 10 adult patients with treated at the Hospital of the University of Pennsylvania (HUP) and two children with treated at the Children's Hospital of Philadelphia. Two of the first three patients treated with the protocol at HUP – whose cases were detailed in the and Science Translational Medicine in August 2011 – remain healthy and in full remissions more than two years after their treatment, with the engineered cells still circulating in their bodies. The findings reveal the first successful and sustained demonstration of the use of to turn the body's own immune cells into weapons aimed at .

"Our results show that chimeric modified T cells have great promise to improve the treatment of leukemia and lymphoma," says the trial's leader, Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penn's Abramson Cancer Center. "It is possible that in the future, this approach may reduce or replace the need for ."

The results pave the way for a potential paradigm shift in the treatment of these types of blood cancers, which in advanced stages have the possibility of a cure only with . That procedure requires a lengthy hospitalization and carries at least a 20 percent —and even then offers only a limited chance of cure for patients whose disease has not responded to other treatments.

Three abstracts about the new research will be presented during the ASH meeting. David Porter, MD, director of Blood and Marrow Transplantation in the Abramson Cancer Center, will give an oral presentation of Abstract #717 on Monday, Dec. 10, at 5 PM in the Thomas Murphy Ballroom 4, Level 5, Building B of the Georgia World Congress Center. Michael Kalos, PhD, director of the Translational and Correlative Studies Laboratory at Penn, will give an oral presentation on Abstract #756 on Monday, Dec. 10, at 5:45 PM in C208-C210, Level 2, Building C. Stephan Grupp, MD, PhD, director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia, will present a poster of Abstract #2604 on Sunday, Dec. 9, at 6 PM in Hall B1-B2, Level 1, Building B.

The protocol for the new treatment involves removing patients' cells through an apheresis process similar to blood donation, and modifying them in Penn's cell and vaccine production facility. Scientists there reprogram the patients' T cells to target tumor cells through a gene modification technique using a HIV-derived lentivirus vector. The vector encodes an antibody-like protein, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T cells and designed to bind to a protein called CD19.

The modified cells are then infused back into the patient's body following lymphodepleting chemotherapy. Once the T cells start expressing the CAR, they focus all of their killing activity on cells that express CD19, which includes CLL and ALL tumor cells, and normal B cells. All of the other cells in the patient that do not express CD19 are ignored by the modified T cells, which limits systemic side effects typically experienced during traditional therapies.

In addition to initiating the death of the cancer cells, a signaling molecule built into the CAR also spurs the cell to produce cytokines that trigger other T cells to multiply—building a bigger and bigger army until all the target cells in the tumor are destroyed.

In the patients who experienced complete remissions after treatment, the CAR T cells exhibited vigorous proliferation after infusion, with the most robust expansion activity usually occurring between 10 and 31 days after infusion. Each of these patients developed a cytokine release syndrome—marked by fever, nausea, hypoxia and low blood pressure—which doctors treated when needed with the anti-cytokine agent tocilizumab.

Ultimately, the modified T cell treatment eradicated large amounts of tumor in these patients.

Tests of patients with complete responses also show that normal B cells have been eliminated along with their tumors. Since these are important for the body's immune system to fight infection, the patients now are receiving regular gamma globulin treatments as a preventive measure. No unusual infections have been observed.

Explore further: Modified killer T-cells wipe out leukemia: study

Related Stories

Modified killer T-cells wipe out leukemia: study

August 10, 2011
Three US cancer patients were brought back from the brink by a new therapy that turned their own immune cells into tumor killers, wiping out an advanced form of leukemia, researchers said Wednesday.

Genetically modified T cell therapy shown to be safe, lasting in decade-long study of HIV patients

May 2, 2012
HIV patients treated with genetically modified T cells remain healthy up to 11 years after initial therapy, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the new issue of Science ...

Researchers repair immune system in leukemia patients following chemotherapy

December 12, 2011
A new treatment using leukemia patients' own infection-fighting cells appears to protect them from infections and cancer recurrence following treatment with fludarabine-based chemotherapy, according to new research from the ...

Gene-modified stem cells help protect bone marrow from toxic side effects of chemotherapy

May 21, 2011
Although chemotherapy is used to kill cancer cells, it can also have a strong toxic effect on normal cells such as bone marrow and blood cells, often limiting the ability to use and manage the chemotherapy treatment. Researchers ...

Recommended for you

Researchers release first draft of a genome-wide cancer 'dependency map'

July 27, 2017
In one of the largest efforts to build a comprehensive catalog of genetic vulnerabilities in cancer, researchers from the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have identified more than 760 genes ...

Cancer-death button gets jammed by gut bacterium

July 27, 2017
Researchers at Michigan Medicine and in China showed that a type of bacterium is associated with the recurrence of colorectal cancer and poor outcomes. They found that Fusobacterium nucleatum in the gut can stop chemotherapy ...

Long-sought mechanism of metastasis is discovered in pancreatic cancer

July 27, 2017
Cells, just like people, have memories. They retain molecular markers that at the beginning of their existence helped guide their development. Cells that become cancerous may be making use of these early memories to power ...

Manmade peptides reduce breast cancer's spread

July 27, 2017
Manmade peptides that directly disrupt the inner workings of a gene known to support cancer's spread significantly reduce metastasis in a mouse model of breast cancer, scientists say.

Blocking the back-door that cancer cells use to escape death by radiotherapy

July 27, 2017
A natural healing mechanism of the body may be reducing the efficiency of radiotherapy in breast cancer patients, according to a new study.

Glowing tumor technology helps surgeons remove hidden cancer cells

July 27, 2017
Surgeons were able to identify and remove a greater number of cancerous nodules from lung cancer patients when combining intraoperative molecular imaging (IMI) - through the use of a contrast agent that makes tumor cells ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.