Gene Therapy progress to cures for adult leukemia and Duchenne muscular dystrophy

1. Two of three patients dying of chronic lymphocytic leukemia (CLL) appear cured and a third is in partial remission after infusions of genetically engineered T cells.

The treatment success came in a pilot study that was only meant to find out whether the treatment was safe, and to determine the right dose to use in later studies.

“Our results were absolutely dramatic. It is tremendously exciting,” Porter tells WebMD. “These kinds of outcomes don’t come around very often. We are really hopeful that we can now translate this into treatment for much larger numbers of patients and apply this technique to other diseases and to many more patients.”

Excitement is spreading as oncologists learn about the findings. “I think it is a big deal,” says Jacque Galipeau, MD, professor of hematology and medical oncology at Emory University Winship Cancer Center. Galipeau was not involved in the Porter study.

“Here’s this guy, the handwriting is on the wall, any hematologist will tell you he is a goner — this guy was essentially cured,” Galipeau tells WebMD. “These genetically engineered cells did what everyone in the field has tried to do for 20 years. The man probably had kilograms of disease in his body, and the cells mopped it up completely.”

The treatment uses a form of white blood cells called T cells harvested from each patient. A manmade virus-like vector is used to transfer special molecules to the T cells. One of the molecules, CD19, makes the T cells attack B lymphocytes — the cells that become cancerous in CLL.

All this has been done before. These genetically engineered cells are called chimeric antigen receptor (CAR) T cells. They kill cancer in the test tube. But in humans, they die away before they do much damage to tumors.

What’s new about the current treatment is the addition of a special signaling molecule called 4-1BB. This signal does several things: it gives CAR T cells more potent anti-tumor activity, and it somehow allows the cells to persist and multiply in patients’ bodies. Moreover, the signal does not call down the deadly all-out immune attack — the feared “cytokine storm” — that can do more harm than good.

This may be why relatively small infusions of the CAR T cells had such a profound effect. Each of the cells killed thousands of cancer cells and destroyed more than 2 pounds of tumor in each patient.

“Within three weeks, the tumors had been blown away, in a way that was much more violent than we ever expected,” June says in a news release. ‘It worked much better than we thought it would.”

2. Researchers from Japan and Italy have successfully used gene therapy to treat mice with Duchenne muscular dystrophy — a disease that causes muscle deterioration and eventually death — providing hope for clinical application in humans.

The research team was able to restore mobility in mice with the genetic disorder by taking and repairing the mice’s stem cells and then putting them back in the mice’s bodies in a process using human artificial chromosomes.

Duchenne muscular dystrophy affects about one in 3,500 males. It is caused by abnormalities in or a deficiency of dystrophin genes, which are essential for maintaining muscles in the body. Since they are the largest human genes, treatment using viruses to carry normal dystrophin genes into cells had not been conducted in the past.

The team extracted muscle-forming stem cells from a mouse with a dystrophin gene abnormality, and inserted human artificial chromosomes carrying normal human genes into the cells. When these stem cells were multiplied and injected into the arteries of the mice, the mobility of the mice improved, and the treatment remained effective for over 70 percent of the remaining life of the mice.

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