Ready-made CAR T Cells

New method could allow scaled-up production of generic cells for cancer immunotherapies

microscope image shows three green-outlined cells surrounding a round blue cell against a dark backdrop
Killer T cells (green and red) surround a cancer cell (blue, center). Image: Alex Ritter, Jennifer Lippincott Schwartz, and Gillian Griffiths/National Institutes of Health

CAR T-cell immunotherapy is a powerful approach for treating certain leukemias and lymphomas, but it’s not available for many patients who need it. A new technique developed by researchers at Harvard Medical School and Boston Children’s Hospital could make CAR T-cell therapy more widely accessible.

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Findings are described Aug. 4 in Cell Stem Cell.

In CAR T-cell therapy, T cells from a patient’s own blood are engineered to carry so-called chimeric antigen receptors, or CARs, that enhance the T cells’ ability to attack and kill tumor cells.

It can be difficult to gather enough functional T cells from patients’ blood, and manufacturing CAR T cells for each individual patient is expensive and takes time—time patients may not have on their side.

The new technique—developed by the lab of George Q. Daley, a member of the Boston Children’s Stem Cell Program and the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and colleagues—uses induced pluripotent stem cells (iPS cells) to make generic CAR T cells that could be produced at scale for use in multiple patients.

“We show that generic iPS cells can be converted to CAR T cells not only more efficiently, but more effectively—creating an enhanced CAR T cell that more faithfully resembles the gold-standard clinical-grade cells we currently use,” said senior author Daley, who is also the Caroline Shields Walker Professor of Medicine in the Blavatnik Institute at HMS, dean of HMS, and professor of pediatrics at Boston Children’s. “Our strategy could enable ‘off-the-shelf’ CAR-T therapies and help more patients access these treatments.”

Enhanced antitumor activity

While iPS cells are, in theory, a limitless source of different cell types, Daley, first author Ran Jing, research fellow in pediatrics at Boston Children’s, and colleagues had to overcome the challenge of deriving mature, fully functioning T cells from which CAR T cells could be made. In the past, researchers have struggled with this because of the tendency for iPS cells to produce immature, embryonic cells in the petri dish.

After many years of promise, it seems that iPS cells are finally yielding new therapeutic approaches to the treatment of diseases like cancer.

George Q. Daley