Less than two years after the FDA first approved Novartis and Gilead’s groundbreaking autologous CAR-T treatments, the next revolution in cancer cell therapy is already raging on as biotechs like Cellectis and Allogene begin testing products made from healthy donor cells. UCLA scientists want to take the off-the-shelf approach one step further by growing a “virtually unlimited supply” of T cells in the lab.
The technique, which involves turning pluripotent stem cells into mature T cells, uses bespoke structures called artificial thymic organoids — a simulation of the environment where blood stem cells develop into T cells in the body. The publication of the technique in Cell Stem Cell back in January was a boon for Gilead’s Kite, which licensed the method for cancer therapy.
“Once we create genetically edited pluripotent stem cell lines that can produce tumor-specific T cells in artificial thymic organoids, we can expand those stem cell lines indefinitely,” said Amélie Montel-Hagen, the study’s first co-author.
Assuming these cells can be properly tuned with gene editing to go after different tumor types and prevent immune reactions from the patient — a big assumption given the early stage of research — it could represent a big leap from currently available CAR-T therapies that can only be manufactured one at the time, with the patients’ own T cells, to varying efficacy.
It is, however, unclear how the manufacturing efficiency and accessibility would compare with other allogeneic CAR-Ts in development. Allogene, which unveiled some impressive complete response rates for its therapy at ASH last year, says its process has potential to treat around 100 patients from a single manufacturing run.
Still, the fact that the team starts with pluripotent stem cells is what makes the approach exciting, said Gay Crooks, director of UCLA’s Cancer and Stem Cell Biology Program and senior author of the study,
Their next step, the researchers say, will be to create T cells that possess cancer-fighting receptors but not molecules that cause rejection of the cells.
This isn't totally novel. $FATE will have an IND for iPSC derived CAR-T in the coming months. Already has one approved for NK cells.
— Brad Loncar (@bradloncar) February 21, 2019
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