Designer Cell

A British baby cured of leukemia has researchers hopeful that a new therapy may be used soon to treat others like her.

The girl, 1-year-old Layla, was diagnosed with an incurable form of cancer in her bone marrow.

She was given an experimental therapy at Britain's Great Ormond Street Hospital (GOSH) to treat her acute lymphoblastic leukemia.

The therapy, chimeric antigen receptor 19 T-cells (CAR-T), used edited genes to boost her T-cells, the main immune cells that target and kill cancer cells.

Two months later, Layla was deemed cleared of her cancer and sent home with her mother, father, and older sister.

Gene editing is one of the latest forms of immunotherapy, but the kind used to treat Layla was a bit different. It used technology dubbed TALEN by its makers, Cellectis.

TALEN works as “molecular scissors” to make the T-cells invisible to a cancer drug that would normally kill them. They then are reprogrammed to fight only leukemia.

The research, unveiled at the annual meeting of the American Society of Hematology, offers new pathways for cancer-fighting drugs. Researchers say this early evidence for ready-made T-cells means the therapy can now be tested in early phase clinical trials.

Using Another Person’s Genes

The difference in this case, unlike other gene editing therapies, is that the cells used in the therapy weren’t from Layla but rather from a different person.

This approach would allow pharmaceutical companies to mass-produce these therapies to treat leukemia and other cancers without the cumbersome and costly process of editing an individual patient’s genes.

Waseem Qasim, Ph.D., consultant immunologist at GOSH and professor of cell and gene therapy at University College London (UCL) Institute of Child Health, was the one who requested the CAR-T therapy for use in Layla.

He called her case “a landmark in the use of new gene engineering technology.”

“If replicated in other patients, it could represent a huge step forward in treating leukemia and other cancers,” he said in a press release.

While the findings are encouraging, the CAR-T therapy is still classified as an unlicensed investigational medicine. This means there are months, if not years, of research needed into the safety and efficacy before it would be available to other cancer patients.

While Layla’s is the first “in-man” case of using an outside donor’s cells, other cases of CAR-T-based therapies have previously been effective at attacking leukemia tumors.

A 2011 study published in the New England Journal of Medicine followed three patients with chronic lymphoid leukemia treated with CAR-T therapies who were still in remission 10 months after treatment.

The cells used in these patients, however, were from the patients themselves and not from a universal donor.

CRISPR Is Popular Now

CRISPR, which stands for clustered regularly interspaced short palindromic repeats, is another method of gene editing that’s been rising in popularity. That system is cheap, quick, easy to use, and doesn’t require years of training.

Its availability “is causing a major upheaval in biomedical research,” but bioethicists are worried about the breakneck speed that researchers are clamoring to use it, especially to edit human embryos, according to the journal Nature.

Cellectis CEO André Choulika says gene editing with CRISPR is more of a service and less of a product, while CAR19 T-cells can be mass-produced.

“[CRISPR] is cheap to design and quick to design. One week and 10 bucks. Any academic researcher can order CRISPR online and become a gene editor,” Choulika told FierceBiotech in June. “[But] its efficiency is really bad.”

While TALEN has already saved one life with the potential to save more, its eventual price tag remains a mystery.

Pfizer Snatches up CAR-T Technology

In June, pharmaceutical giant Pfizer announced that it had entered into a global strategic collaboration with Cellectis to develop CAR-T immunotherapies.

Under the agreement, Pfizer will have exclusive commercial rights to develop CAR-T therapies for 15 targets of Pfizer’s choosing. Cellectis is allowed to pick 12.

Together, the companies will conduct preclinical research on four targets Cellectis chooses (while Pfizer retains first refusal rights), while Cellectis works independently on eight targets of its choosing.

This agreement netted Cellectis $80 million, along with funding for costs related to the targets Pfizer chooses and up to another $185 million per drug after drugs are developed in the future. Pfizer’s revenues will come when products and services are sold.

Dr. Mikael Dolsten, president of research and development at Pfizer, said his company’s cutting-edge biotherapeutic cancer therapy technology coupled with Cellectis’ genome editing and cell engineering will provide new immunotherapies.

“Combining the innovation and scientific expertise of Cellectis with Pfizer’s deep oncology and immunology experience creates a world-class partnership designed to deliver a new generation of CAR-T immunotherapies for cancer patients with urgent medical needs,” he said in a press release.