Scientists at UC San Francisco announced on March 19 a new method to reprogram cancer-fighting immune cells directly inside the body, potentially making advanced therapies more accessible and affordable for patients with certain blood cancers.
The development could address significant barriers in current CAR-T cell therapy, which requires extracting a patient’s immune cells, modifying them in specialized facilities, and reinfusing them—a process that is costly and time-consuming. The new approach may allow for broader access to these treatments.
According to the researchers, this is the first time a large DNA sequence has been integrated at a specific site in human T cells without removing them from the body. In experiments using mice with humanized immune systems, the team successfully treated aggressive leukemia, multiple myeloma, and even a solid tumor. “I think this is just the beginning of a big wave of new therapies that will be truly transformational and save a lot of lives,” said Justin Eyquem, Ph.D., associate professor of medicine at UCSF and senior author of the study. “I’m incredibly excited to be part of it.”
The method uses two types of particles: one delivers CRISPR-Cas9 gene-editing machinery to T cells circulating in the body; the other carries new DNA for chimeric antigen receptors (CARs), which enable T cells to recognize and attack cancer cells. This targeted approach avoids random integration of genes—a risk factor for secondary cancers—and ensures only T cells are genetically altered. “When you manufacture these cells outside the body, you can do a lot of quality control… We can’t do that inside the body, so we really needed to optimize the approach upfront to avoid genetically altering any other cells,” Eyquem said.
In mouse studies led by William Nyberg, Ph.D., and Pierre-Louis Bernard, Ph.D., nearly all mice with aggressive leukemia were cleared of detectable cancer within two weeks after receiving a single injection. The engineered CAR-T cells also performed well against multiple myeloma and solid sarcoma tumors—an area where traditional CAR-T therapies have struggled. “What was especially remarkable was that the cells we’re generating in vivo actually look better than what we make in the lab,” Eyquem said.
Clinical trials will be necessary before this method can be used in humans. Eyquem and collaborators have founded Azalea Therapeutics to advance clinical development. “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,” he said. “That would truly democratize access to CAR-T cell therapy.”
