A single injection cleared all detectable cancer in nearly every mouse with aggressive leukemia within two weeks. That is the result researchers at UC San Francisco reported in a study published March 18 in Nature, and the way they did it is what makes it notable.
Standard CAR-T therapy takes a patient’s immune cells out, sends them to a specialized lab for genetic modification, and infuses them back. It works for certain blood cancers. It also takes weeks and often costs hundreds of thousands of dollars. Costs typically run $400,000 to $500,000, and seven CAR-T therapies are approved by the U.S. Food and Drug Administration for blood cancers.
The UCSF team skipped the lab. They built a two-particle delivery system that carries CRISPR-Cas9 gene editing tools to T cells in the bloodstream. One particle is coated with antibodies that bind CD3, a protein found only on T cells, so the system finds the right targets. The second holds the DNA instructions for the cancer-fighting receptor and guidance for placing it at a precise spot in the T cell genome.
That spot acts as an “on switch” active only in T cells. It is the first time scientists have placed a large DNA sequence at a precise location in human T cells without taking the cells out of the body, and it outperformed the conventional method of using viruses to insert DNA at random.
What the mice showed
In some organs, the engineered cells made up as much as 40% of immune cells and cleared cancer from the bone marrow and spleen. The method also worked against multiple myeloma and a solid sarcoma tumor. Solid tumors have typically resisted CAR-T therapy.
“What was especially remarkable was that the cells we’re generating in vivo actually look better than what we make in the lab,” said Justin Eyquem, the senior author and an associate professor of medicine at UCSF.
Still years from patients
All of this was in mice with human-like immune systems. The approach has to be adapted for people, and clinical trials will be needed to test safety and effectiveness. Eyquem and his collaborators have started a company, Azalea Therapeutics, to push the technology forward.
If it works in humans, the method could remove the need for chemotherapy beforehand, which is hard on older or medically fragile patients. “If we can translate this to humans, we could dramatically reduce costs, eliminate waiting times, and potentially allow community hospitals, not just major cancer centers, to offer these life-saving therapies,” Eyquem said.
Patients with blood cancer should talk to their doctor about the treatments available to them today. Consult your doctor for medical advice.
