Skip to content

Immunotherapy Showed Promising Antileukemia Activity in Pediatric Patients

April 6, 2013
Bookmark and Share
  • Treatment used patients’ own immune cells.
  • After brief manipulation in the laboratory, cells were returned to patients.
  • Treatment was tolerated; three patients with ALL responded.

WASHINGTON, D.C. — Researchers using patients’ own immune cells in an immunotherapy approach called “anti-CD19 chimeric antigen receptor (CAR) T-cell therapy,” achieved responses in children whose acute lymphocytic leukemia (ALL) had returned after a bone marrow transplant, according to preliminary results presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“Anti-CD19 CAR T-cell therapy using patients’ own immune cells is a completely new way of treating childhood cancer,” said Daniel W. Lee, M.D., assistant clinical investigator in the Pediatric Oncology Branch of the National Cancer Institute. “It is not chemotherapy; therefore, it has a different side effect profile — we hope better tolerated. In the limited number of post-transplant patients we have treated so far, we’re getting acceptable toxicities, and we’re not seeing graft-versus-host disease.”

More than 95 percent of children initially diagnosed with ALL achieve remission, but a significant number of them relapse, according to Lee. Once they relapse, the prognosis is poor, with ALL accounting for the most deaths from cancer among children.

Other research teams are testing anti-CD19 CAR T-cell therapy in children with ALL that has returned after a bone marrow transplant, according to Lee. However, whether they are using immune cells from the transplant donor, or collecting and preparing the patient’s cells, the process is lengthy.

“Often these children with relapsed ALL don’t have that kind of time to wait,” Lee said. “We wanted something that could be done in a more timely manner. We decided to collect the immune cells, which are called T cells, directly from the patients, even though they’d had bone marrow transplants.”

The first three patients in the phase I trial had undergone a previous bone marrow transplant, although the trial is also open to patients who have never had a transplant. One patient had B-cell lymphoma and the other two had ALL.

The researchers collected T cells from the patients and modified them in the laboratory so that they would attach to a protein expressed by the leukemia cells, called CD19, and attack the cancers. The number of modified T cells, now called anti-CD19 CAR T cells, was expanded in the laboratory before they were returned to the patients.

The results so far indicate that this approach is a feasible and active treatment for pediatric patients with ALL, even those who relapse after a bone marrow transplant, according to Lee. One patient had a complete response and a second had a transient complete response, with minimal residual disease remaining. The lone lymphoma patient did not respond.

Cell expansion was robust. “We were able to get very good expansion — on average about 60-fold expansion of these cells during the 11-day culture period,” Lee said. “And we were able to insert the receptor, the anti-CD19 CAR, into those T cells with good efficiency.”

One patient did not produce a sufficient number of cells, which was likely related to recent intensive chemotherapy and resultant low T-cell count, according to Lee. Despite this, the few cells the patient did receive expanded dramatically and the patient temporarily achieved remission.

Lee and colleagues continue to test this approach in patients whose disease has returned after, or is refractory to, standard treatments whether or not they have had a bone marrow transplant.

“We think that the children who have never had a transplant might experience different toxicities,” said Lee. “Our first patient enrolled in this arm of the trial had never achieved disease remission after her initial diagnosis of ALL despite intensive chemotherapy. Strikingly, anti-CD19 CAR T-cell therapy resulted in the complete clearance of any detectable leukemia in this patient, and we were able to send her back to her primary oncologists for a bone marrow transplant.”

Lee’s research was partially funded by the St. Baldrick’s Foundation.

# # #

Press registration for the AACR Annual Meeting 2013 is free to qualified journalists and public information officers.

Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:

(202) 249-4005

No comments yet

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: