Genetically engineered T-cells treat leukemia in babies

Researchers in London have successfully treated leukemia in two babies, in what they are touting as the world’s first treatment of cancer using genetically engineered immune cells from donors.Doctors treated two British infants, 11 and 16 months old, using Cellectis’s CAR T-cell product, UCART19, which is an allogeneic CAR T-cell product candidate for the treatment of chronic lymphocytic leukemia and acute lymphoblastic leukemia. They had gone through previous radiation treatments that failed before being treated with Cellectis’ UCART19.

The London’s Great Ormond Street Hospital experiments could be the first step to off-the-shelf cellular therapy using inexpensive supplies of universal cells that can be dripped into veins.

“The patient could be treated immediately, as opposed to taking cells from a patient and manufacturing them,” Julianne Smith, vice president of CAR-T development for Cellectis, said in MIT Technology Review.

Hundreds of doses of engineered blood collected from a donor is stored frozen in off-the-shelf therapy. Engineering a patient’s own blood costs around $50,000.

“We estimate the cost to manufacture a dose would be about $4,000,” Smith said.

More study is needed, however, said Waseem Qasim, a cell and gene therapy professor who carried out the work at the Great Ormond Street Hospital.

“While both patients are now at home and are doing well, we must treat these results with some caution as we don’t yet know if the technique will be successful in treating a larger number of patients,” Qasim said. “Clinical trials are currently underway to assess this.”

The cells that were modified at the Great Ormond Street Hospital went through four genetic changes, two of which were introduced by gene editing using TALENs. The donor cells were stripped of their propensity to attack the body of who the cells were going into. The other gene modification told the cells to attack cancer cells.

Companies like Juno Therapeutics and Novartis have been working on treatments that collect a patient’s own blood cells and engineering them and then re-infusing those cells back into the patient’s body. But the new method uses donor cells.

Both the donor method and using the patient’s own blood use engineered T-cells that attack leukemia cells.

According to the Leukemia and Lymphoma Society, every 3 minutes someone is diagnosed with blood cancer in the U.S. alone. As of 2016, about 345,422 people are living with or in remission from leukemia in the U.S.

Engineered T-cell treatment is not sold commercially, but has had success in treating blood cancers in the past. Previous research showed that when T-cells were removed from the blood and engineered to fight cancer, 90 percent of patients with acute lymphoblastic leukemia had their cancer go away.

Novartis has a manufacturing center in New Jersey that receives patient cells from 25 hospitals accross 11 countries. It modifies those cells and ships them back to the source. Novartis is looking for U.S. approval to sell T-cell treatment for children this year.

Some researchers believe that because the children who were treated also received standard chemotherapy in the past, the experiment failed to show that the cell treatment actually was able to cure them of leukemia.

“There is a hint of efficacy but no proof,” said Stephan Grupp, director of cancer immunotherapy at the Children’s Hospital of Philadelphia and collaborator with Novartis. “It would be great if it works, but that just hasn’t been shown yet.”

Servier acquired the exclusive rights to UCART19 from Cellectis in November of 2015. Servier and Pfizer began collaborating on a joint clinical development program for cancer immunotherapy. Pfizer has the rights to develop and commercialize UCART19 in the U.S. and Servier has the rights for all other countries.

Other companies, like Regeneron, Kite Therapeutics, Fate Therapeutics and Cell Medica, are betting on off-the-shelf cancer treatment.

The research was published online in the Science Translational Medicine magazine.