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Editing genes with CRISPR to make immune cells attack cancer appears safe, Penn study finds

The first step in human drug testing is showing safety. So far, the first approved use of gene editing in U.S. patients has met that goal.

Edward Stadtmauer, chief of the blood cancer section at the University of Pennsylvania
Edward Stadtmauer, chief of the blood cancer section at the University of PennsylvaniaRead moreUniversity of Pennsylvania

Three patients with advanced cancers, treated at the University of Pennsylvania in the first U.S. clinical study of gene editing, have had no serious side effects so far — a reassuring sign that the revolutionary technology can safely be used in humans, according to results released Wednesday.

The inaugural U.S. experiment using CRISPR-edited cells in humans is such a scientific and ethical watershed that Penn spent more than two years getting federal and other approvals. At least three other CRISPR trials — in sickle cell disease, non-Hodgkin’s lymphoma, and an inherited form of blindness — have since gotten go-aheads.

Experimental drugs must show safety in a pilot clinical trial. Then, more patients are treated to look for evidence of effectiveness.

Two of the patients treated at Penn have an incurable bone marrow cancer called multiple myeloma, while the third has a soft tissue cancer called sarcoma. Their cancers overproduce a protein called NY-ESO-1.

In previous research involving 25 patients, Penn researchers showed they could genetically engineer each patient’s own disease-fighting T cells to recognize multiple myeloma cells overloaded with that protein.

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The CRISPR trial is designed to see whether the T cells can be edited to make them more effective. Researchers snipped out two genes that theoretically should enhance the cells’ ability to bind to the cancer cells; a third excised gene should take a natural immune system brake off the T cells.

Edward A. Stadtmauer, the Penn blood cancer specialist who led the study, said, “This trial is primarily concerned with three questions: Can we edit T cells in a specific way? Are the resulting cells functional? And are these cells safe to infuse into a patient? This early data suggest that the answers to all three questions may be yes.”

The results, which Stadtmauer will present Saturday at a hematology convention, show that the edited T cells multiplied, persisted, and homed in on the myeloma cells. However, one patient’s cancer progressed, one has stable disease, and the third was treated too recently to evaluate.

Over the next four years, the trial aims to treat 18 patients with advanced myeloma, sarcoma, and melanoma.

Penn gene therapy pioneer Carl June, who led the studies behind the world’s first T-cell cancer therapy, stressed that CRISPR is not being used to directly alter the patients’ genomes. Last year, a Chinese researcher was denounced as reckless after he claimed to have used CRISPR to alter the genetic code of two human babies to make them immune to the AIDS virus.

“Our use of CRISPR is geared toward improving the effectiveness of gene therapies, not editing a patient’s DNA,” June said.

The trial is being funded by the Parker Institute for Cancer Immunotherapy — an initiative of billionaire tech guru Sean Parker — and Tmunity, a biotech company cofounded by June. The University of Pennsylvania, June, and other Penn scientists have financial interests in the company.