person treated with UCART19
Photo courtesy of GOSH
A hospital in the UK has reported success with the first-in-human use of an allogeneic chimeric antigen receptor (CAR) T-cell treatment.
The therapy, UCART19, helped treat an aggressive case of acute lymphoblastic leukemia (ALL) in an infant named Layla Richards.
Chemotherapy, a first transplant, and blinatumomab all failed to treat Layla’s disease. But UCART19 provided a bridge to a second transplant, and Layla
is now free of leukemia.
“We have only used this treatment on one very strong little girl, and we have to be cautious about claiming that this will be a suitable treatment option for all children,” said Waseem Qasim, MBBS, PhD, a professor at University College London’s Institute of Child Health and a consultant immunologist at Great Ormond Street Hospital (GOSH) in London, where Layla was treated.
“But this is a landmark in the use of new gene-engineering technology, and the effects for this child have been staggering. If replicated, it could represent a huge step forward in treating leukemia and other cancers.”
Layla’s history
Layla was born in June 2014 and, at 14 weeks old, was diagnosed with CD19+ ALL (t[11;19] rearrangement). Doctors at GOSH described her leukemia as “one of the most aggressive forms of the disease we have ever seen.”
Layla underwent several rounds of chemotherapy at GOSH and then received a transplant from a mismatched, unrelated donor. Seven weeks later, her leukemia had returned.
A second round of chemotherapy wasn’t an option, so Layla went on to receive blinatumomab. This, too, ultimately failed.
Layla’s family was unwilling to accept palliative care, so her doctors mentioned the possibility of using UCART19.
“The approach was looking incredibly successful in laboratory studies, and so when I heard there were no options left for treating this child’s disease, I thought, ‘Why don’t we use the new UCART19 cells?’” Dr Qasim said.
“The treatment was highly experimental, and we had to get special permissions, but she appeared ideally suited for this type of approach.”
UCART19 treatment
Before Layla received UCART19, investigators from GOSH, University College London, and the biotech company Cellectis had been developing off-the-shelf banks of the cells for use in clinical trials.
UCART19 consists of donor T cells modified using transcription activator-like effector nucleases (TALEN). Like some other CAR T-cell products, UCART19 is designed to target CD19+ cancer cells.
But UCART19 cells are also programmed to be insensitive to alemtuzumab. That way, a patient can receive the drug to prevent rejection of HLA-mismatched cells.
Before receiving UCART19, Layla was given vincristine, dexamethasone, and asparaginase, followed by fludarabine, cyclophosphamide, and alemtuzumab. She then received a single dose (4.5 x 106/kg) of UCART19.
After this, Layla spent several months in isolation to protect her from infections while her immune system was extremely weak. Within weeks of receiving UCART19, Layla demonstrated an immune response in the form of a rash.
The rash worsened, but, aside from that, Layla appeared to be well. To date, she has shown no signs of cytokine release syndrome.
She did, however, show signs of molecular and cytogenetic remission. Once she was deemed leukemia-free, Layla underwent a second transplant. One month later, she was well enough to go home. Today, Layla is still free of ALL.
More details on Layla’s story and UCART19 are scheduled to be presented at the 2015 ASH Annual Meeting (abstract 2046). Clinical trials of UCART19 (funded by Cellectis) are set to begin early next year.
