Scientists at the University of California, San Francisco (UCSF) have developed a method to reprogram immune cells directly inside the body to fight cancer. This approach, known as in vivo CAR-T therapy, could remove the need for complex manufacturing processes that currently limit access to these treatments.
Standard CAR-T cell therapy requires doctors to collect a patient’s T cells, send them to a specialized facility for genetic modification, and then infuse the engineered cells back into the patient. The process takes weeks and costs between $400,000 and $500,000. It also requires patients to undergo intensive chemotherapy to clear space in their bone marrow before receiving the new cells.
Direct Gene Editing in Humanized Mice
The new technique, described in the journal Nature, uses two different particles to deliver CRISPR-Cas9 gene-editing machinery directly to T cells circulating in the bloodstream. One particle carries the gene-editing tools and targets CD3, a protein found only on T cells. The second particle delivers the DNA instructions for creating chimeric antigen receptors (CARs) and directs them to a precise location in the T cell genome.
In experiments with mice that had humanized immune systems, the team successfully treated aggressive leukemia, multiple myeloma, and a solid sarcoma tumor. After a single injection, detectable cancer disappeared in nearly all mice within two weeks. In some organs, the newly engineered CAR-T cells made up as much as 40% of the immune cell population.
Justin Eyquem, PhD, an associate professor of medicine at UCSF and the senior author of the study, noted that the cells generated inside the body performed better than those produced in the lab. He suggested that removing cells from the body causes them to lose some of their proliferative capacity, a problem avoided by this in vivo method.
Reducing Costs and Wait Times
Current CAR-T therapies are limited by their high cost and the time required for manufacturing. Many patients cannot afford the treatment or cannot wait weeks for their cells to be modified while their cancer progresses. The in vivo approach could potentially eliminate the need for preparatory chemotherapy and reduce the reliance on specialized manufacturing facilities.
If translated to humans, this method could allow community hospitals to offer these therapies, not just major cancer centers. Eyquem stated that the goal is to democratize access to CAR-T cell therapy by dramatically reducing costs and eliminating waiting times.
The research team, including co-first authors William Nyberg, PhD, and Pierre-Louis Bernard, PhD, emphasized the importance of precision. Because quality control cannot be performed after the cells are modified inside the body, the system was designed to avoid altering any other cells. The particles were also engineered to avoid immediate destruction by the immune system.
The technology is not yet ready for human patients. Researchers must scale up the approach and conduct clinical trials to determine its safety and efficacy in people. To move the dual-particle platform toward clinical development, Eyquem and his collaborators have founded Azalea Therapeutics.
Source: ScienceDaily
