Scientists have achieved a breakthrough in cancer immunotherapy by successfully engineering CAR T-cells directly inside the bodies of laboratory animals, potentially transforming one of medicine's most promising but expensive cancer treatments. The research, led by Carl June at the University of Pennsylvania, demonstrates that CAR T-cell therapy can be created in vivo rather than through costly and time-consuming laboratory manufacturing processes.
Revolutionary Approach Eliminates Manufacturing Bottlenecks
Traditional CAR T-cell therapy involves collecting T-cells from patients, shipping them to specialized manufacturing facilities for genetic engineering, and then returning the modified cells weeks later. This process can cost upwards of $500,000 per patient and creates significant delays for cancer patients who need immediate treatment.
"You've got to take blood, ship it to a central manufacturing lab and then return [the T-cells]," explains June. "That means it's very hard to scale up." The manufacturing complexity has been identified as a major barrier, with recent studies showing that producing a single batch can cost between $170,000 and $220,000.
In Vivo Engineering Shows Dramatic Results
The Pennsylvania team developed an innovative approach using RNA molecules packaged in fatty capsules coated with proteins that specifically target T-cells. These capsules carry genetic instructions to create proteins that recognize and destroy B-cells, the cancerous cells targeted in certain blood cancers.
In their animal studies, researchers injected cancerous human B-cells and healthy human T-cells into immunocompromised mice. After administering five doses of the fatty capsules over approximately two weeks, mice receiving the highest dose showed complete tumor elimination three weeks later. "Tumour cell levels were as close as we can detect to being eliminated," June reported.
Primate Studies Demonstrate Rapid Efficacy
The approach proved even more dramatic in primate testing. When the team injected the fatty capsules into 22 healthy monkeys, the treatment generated CAR T-cells that completely cleared all B-cells within just one day. The treatment was well tolerated in all but one monkey, which experienced a severe inflammatory reaction.
Clinical Translation Already Underway
The promising preclinical results have accelerated the path to human testing. June confirmed that clinical trials in healthy humans have already begun, stating, "The first person was dosed in the past few weeks."
Addressing Treatment Limitations
While the approach offers significant advantages in cost and accessibility, it also presents new challenges. Unlike traditional CAR T-cells that can provide long-term protection, the new method only temporarily produces engineered cells, as the RNA code degrades within about a week. This means patients may require repeated injections if cancer returns.
"This is really impressive," says Karin Straathof at University College London. "It is a potentially much simpler procedure for making CAR T-cell therapy, which could make it more affordable." However, she notes that the temporary nature of the treatment and the need for clinical validation remain important considerations.
Transforming Cancer Care Access
The development addresses a critical healthcare challenge, as current CAR T-cell therapy is primarily available in countries like the UK and US for specific blood cancers, including certain types of leukemia where B-cells grow uncontrollably. The high costs and manufacturing complexity have limited patient access to this potentially life-saving treatment.
As Saar Gill, a hematologist and oncologist at the Perelman School of Medicine, points out the current inefficiency: "If I've got a patient with cancer, I can prescribe chemotherapy and they'll get it tomorrow." With commercial CAR T therapy, however, patients must wait weeks for treatment, a delay that could prove critical for rapidly progressing cancers.
The in vivo approach could democratize access to CAR T-cell therapy by eliminating manufacturing bottlenecks and reducing costs, potentially bringing this powerful immunotherapy to a much broader patient population worldwide.
