Two leukemia babies in remission after injection of new kind of edited T-cells

January 26, 2017 by Bob Yirka, Medical Xpress report

Engineered CAR T cell therapy kept two infants with acute lymphoblastic lymphoma in longterm remission. Credit: Val Altounian / Science Translational Medicine (2017)
(Medical Xpress)—Two babies given an experimental kind of edited T-cells to treat their leukemia remain in remission after more than a year, doctors working on the case report in a paper published in the journal Science Translational Medicine. The research team is affiliated with several institutions in the U.K.

The cells used to treat the two babies were part of a modified form of CAR-T cell therapy, in which a virus is used to edit a gene in an immune cell taken from the patient to cause it to attack —once ready, it is injected back into the patient. This approach has been found to be quite successful in a number of children, but is not nearly as applicable to sick infants with low numbers of healthy immune cells. In this new effort, the researchers started with immune cells from a donor and then modified them in several important ways.

The first change was to disable the gene responsible for causing the to attack the donated cell after recognizing it as a foreign body. Another change caused the edited cells to recognize and attack cancer cells. A third change was part of an effort to offset the likelihood of the recipient developing graft-versus-host disease.

The first recipient of the experimental cells was an 11-month-old girl who received her edited cells in June of 2015—she was followed by a 16-month-old child who was injected in December of 2015. Both of the girls also underwent chemotherapy. They also received after a period of time to restore their immune systems and to flush the edited cells from their bodies. One of the babies developed graft-host disease despite the gene change, which was promptly resolved with treatment. Both girls are now home with their families and are reportedly in good health.

The treatment was experimental, which means it has not been approved for use by governmental agencies—it was only allowed in this case because all other options had been exhausted. Trials of various forms of CAR-T cell therapy are ongoing, some of which have shown great promise, suggesting that some may be approved soon.

Explore further: Chinese team to pioneer first human CRISPR trial

More information: Waseem Qasim et al. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells, Science Translational Medicine (2017). DOI: 10.1126/scitranslmed.aaj2013

Abstract
Autologous T cells engineered to express chimeric antigen receptor against the B cell antigen CD19 (CAR19) are achieving marked leukemic remissions in early-phase trials but can be difficult to manufacture, especially in infants or heavily treated patients. We generated universal CAR19 (UCART19) T cells by lentiviral transduction of non–human leukocyte antigen–matched donor cells and simultaneous transcription activator-like effector nuclease (TALEN)–mediated gene editing of T cell receptor α chain and CD52 gene loci. Two infants with relapsed refractory CD19+ B cell acute lymphoblastic leukemia received lymphodepleting chemotherapy and anti-CD52 serotherapy, followed by a single-dose infusion of UCART19 cells. Molecular remissions were achieved within 28 days in both infants, and UCART19 cells persisted until conditioning ahead of successful allogeneic stem cell transplantation. This bridge-to-transplantation strategy demonstrates the therapeutic potential of gene-editing technology.

Related Stories

Chinese team to pioneer first human CRISPR trial

July 22, 2016
(Medical Xpress)—A team of researchers at Sichuan University's West China Hospital has announced plans to begin a clinical trial where cells modified using the CRISPR gene editing technique will be used on human beings ...

Chinese group injects CRISPR edited cells into human test subject for first time

November 16, 2016
(Phys.org)—A team of researchers working at West China Hospital in Chengdu has for the first time injected CRISPR–Cas9 edited cells into a human test subject. Nature reports that the procedure occurred on October 28, ...

Researchers develop new strategy to limit side effects of stem cell transplants

August 15, 2016
Scientists in Germany have developed a new approach that may prevent leukemia and lymphoma patients from developing graft-versus-host disease (GvHD) after therapeutic bone marrow transplants. The researchers describe the ...

Researchers develop novel treatment to prevent graft-versus-host-disease

January 11, 2017
Graft-versus-host-disease (GVHD) is the leading cause of non-relapse associated death in patients who receive stem cell transplants. In a new study published as the cover story in Science Translational Medicine, Moffitt Cancer ...

One-time treatment rescues lethal metabolic liver disease in mice

August 31, 2016
To treat the liver disorder tyrosinaemia type I, one of the most severe forms of the disease, doctors typically use drug therapy. However the treatment is lifelong and a residual risk of liver cancer persists, which is usually ...

Safety switch preserves beneficial effects of cell therapy

May 14, 2015
Researchers in the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston Methodist and Texas Children's Hospital have found that a single dose of an otherwise harmless drug can safely control the severe ...

Recommended for you

Traditional chemotherapy superior to new alternative for oropharyngeal cancers

November 16, 2018
A drug increasingly used in combination with radiotherapy to treat a type of cancer that forms in the tonsils or the base of the tongue is inferior to a previously favored option, according to a large, clinical trial led ...

Repurposing FDA-approved drugs can help fight back breast cancer

November 16, 2018
Screening Food and Drug Administration (FDA)-approved compounds for their ability to stop cancer growth in the lab led to the finding that the drug flunarizine can slow down the growth of triple-negative breast cancer in ...

Standard chemotherapy treatment for HPV-positive throat cancer remains the most effective, study finds

November 15, 2018
A new study funded by Cancer Research UK and led by the University of Birmingham has found that the standard chemotherapy used to treat a specific type of throat cancer remains the most effective.

New 'SLICE' tool can massively expand immune system's cancer-fighting repertoire

November 15, 2018
Immunotherapy can cure some cancers that until fairly recently were considered fatal. In addition to developing drugs that boost the immune system's cancer-fighting abilities, scientists are becoming expert at manipulating ...

Anti-malaria drugs have shown promise in treating cancer, and now researchers know why

November 15, 2018
Anti-malaria drugs known as chloroquines have been repurposed to treat cancer for decades, but until now no one knew exactly what the chloroquines were targeting when they attack a tumor. Now, researchers from the Abramson ...

Researchers identify a mechanism that fuels cancer cells' growth

November 14, 2018
Scientists at the UCLA Jonsson Comprehensive Cancer Center have identified sodium glucose transporter 2, or SGLT2, as a mechanism that lung cancer cells can utilize to obtain glucose, which is key to their survival and promotes ...

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.