A major advancement in gene therapy has made it possible to reprogram immune cells directly inside the body to target tumors, potentially offering more accessible and cost-effective cancer treatments. For several years, therapies have transformed the treatment of certain blood cancers by reprogramming a patient's immune cells to attack tumors. However, the production of these therapies has remained lengthy, complex, and extremely costly. A new development in in-body produced CAR-T therapy could change this dynamic. Current CAR-T therapies involve a multi-step process. Doctors first extract T lymphocytes, a type of white blood cell involved in immune defense, from the patient. These cells are then modified in the laboratory to include an artificial receptor called CAR, which allows them to recognize and attack cancer cells. The modified cells are then re-injected into the patient. This process can take several weeks and cost between $400,000 and $500,000 per patient in the United States. It requires specialized facilities, which are only available at large cancer centers. Additionally, patients must undergo preparatory chemotherapy to make space in their bone marrow before receiving the modified cells. A team led by Justin Eyquem, an associate professor of medicine at the University of California, San Francisco (UCSF), has developed a radically different method. As reported in Nature, their system uses two particles injected directly into the blood. The first carries the CRISPR-Cas9 genetic editing machinery, which targets circulating T lymphocytes in the body. The second delivers the DNA of the anti-cancer CAR receptor. The results in mice have been impressive. According to UCSF, a single injection of the two-particle system was enough to eliminate all detectable traces of leukemia in nearly all treated mice, within less than two weeks. The method has also been effective against multiple myeloma, another blood cancer. More notably, it has shown the ability to reduce solid tumors of the sarcoma type, a cancer that traditional CAR-T therapies generally fail to treat due to the complex defense mechanisms of solid tumors. In some organs, the CAR-T cells produced in the body represented up to 40% of the immune cells present. In essence, the mouse's body becomes the production site for the treatment. According to Justin Eyquem, the cells modified directly in the body "seem even better than those we manufacture in the laboratory." The integration of the CAR DNA occurs at a precise location in the genome, guided by CRISPR. This precision is a major safety advantage. Current methods insert the CAR gene at a random location in the genome, which, in rare cases, can lead to secondary cancers. The technique developed by the UCSF team aims to eliminate this risk by targeting a predefined location in the genome. The study, published on March 18 in Nature, involved researchers from UCSF, the Gladstone Institutes, Duke University, and the Innovative Genomics Institute, co-founded by Jennifer Doudna, a Nobel prize laureate for her work on CRISPR. The team has already formed the company Azalea Therapeutics to advance this technology toward human clinical trials. If the method is confirmed to work in humans, it could significantly reduce manufacturing costs and waiting times. A simple injection could replace weeks of laboratory manipulation. Justin Eyquem estimates that this approach could allow local hospitals, not only large cancer centers, to provide these vital therapies. Currently, seven CAR-T therapies are approved by the American FDA to treat blood cancers. None are effective against solid tumors, which make up the vast majority of cancers diagnosed each year worldwide. The results obtained against sarcomas in mice are encouraging for researchers. However, the transition to human use will still require several years of rigorous clinical trials to evaluate the safety and effectiveness of the system.