Genetically engineered cell therapies may bring hope to patients for whom standard treatments have been unsuccessful, according to two separate studies presented at the 2013 American Society of Hematology (ASH) Annual Meeting, December 7-10, 2013, in New Orleans, Louisiana.

A retroviral vector has been used to treat children with the fatal inherited disease, X-linked severe combined immunodeficiency (SCID-X1, or bubble boy disease). The vector attaches to the surface of a T-cell and injects the missing gene, which integrates into the patient’s DNA and helps to train the T cells to produce their own immune cells.

In previous studies, some children developed leukemia when the new gene inadvertently inserted near a trigger for leukemia. To overcome this, a modified vector was developed that inserts the DNA but does not encourage overgrowth of the T cells. Nine boys with SCID-X1 had some of their bone marrow stem cells removed. The stem cells were treated with the new vector and then infused back into each donor’s bloodstream. Seven of the boys appeared to be producing healthy T cells. Analysis of insertion patterns in the T cells showed that the therapeutic gene ended up inserted near the trigger point for leukemia less frequently than in the previous trial.

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“Using this new vector approach is just as effective but may eliminate the long-term risk of leukemia,” said Sung-Yun Pai, MD, of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Boston, Massachusetts.

In another advance in cell engineering, processing of haploidentical (half-matched) stem cells prior to transplantation could make this treatment accessible to a much wider range of patients. 

Transplantation with haploidentical stem cells has been associated with an increased risk of infection and disease recurrence when compared with transplantation from a fully matched donor. In this second study, alpha/beta-positive T cells and CD19-positive B cells were removed from the donor graft before infusion. These cells are more likely to trigger donor cells to attack recipient cells, leading to graft-versus-host disease (GVHD). This process preserved healthy natural killer and gamma/delta-positive T cells, which help prevent disease relapse and protect against infection.

Forty-five patients with acute leukemia were treated with enhanced stem cells from one of their parents. The transplants were successful in 44 of the 45 patients, and there was a 29% cumulative incidence of mild GVHD. One month after transplant, follow-up analyses showed that transplanted cells persisted in the patients and had potential antileukemic activity that increased over time.

“Our results demonstrate that transplantation of selectively modified, half-matched donor stem cells boasts success rates equivalent to those of a fully matched transplant,” said Alice Bertaina, MD, of the Bambino Gesu Children’s Hospital in Rome, Italy. “This has the potential to make this lifesaving treatment more accessible to a much larger population of patients who may not have a perfect donor match.”