Can Immune Cells Be Reprogrammed Directly in the Body to Fight Cancer?
Researchers have developed an innovative method to genetically modify immune cells, known as T lymphocytes, directly within the body. This breakthrough could make cancer therapies and certain autoimmune disease treatments more accessible, effective, and affordable.
Currently, therapies using modified T lymphocytes, such as CAR-T cells, are already used to treat certain blood cancers. However, their production is complex, time-consuming, and expensive. It requires extracting cells from the patient, modifying them in a laboratory, and then reinjecting them. This new approach bypasses these obstacles by performing the modification directly inside the body.
Scientists have developed a system using two types of vectors. The first, called an enveloped vector, carries genetic modification tools that specifically target T lymphocytes. The second, a modified adenoviral vector, delivers the therapeutic gene to be inserted. Together, they enable precise integration of a new gene into the DNA of T lymphocytes without affecting other cells.
To improve efficiency and safety, researchers optimized these vectors. They created a version resistant to natural antibodies that could block their action. They also added a molecule that activates T lymphocytes, thereby increasing the number of modifiable cells. Thanks to these improvements, up to 20% of the T lymphocytes present in the spleens of humanized mice were successfully modified.
The reprogrammed T lymphocytes demonstrated their ability to eliminate cancer cells in several disease models. They controlled the progression of leukemias, myelomas, and even a sarcoma, a type of solid tumor. Unlike current methods, this technique produces uniformly active and durable cells, enhancing their effectiveness against tumors.
This approach paves the way for simpler and faster treatments. It avoids the steps of extraction and laboratory culture, reducing costs and delays. Additionally, it could be adapted to other diseases where T lymphocytes play a key role, such as infections or autoimmune diseases.
The results obtained in mice are promising, but further studies in humans will be necessary to confirm its efficacy and safety. If these trials are successful, this technology could revolutionize access to cellular therapies for many patients.
Content References
Official Reference
DOI: https://doi.org/10.1038/s41586-026-10235-x
Title: In vivo site-specific engineering to reprogram T cells
Journal: Nature
Publisher: Springer Science and Business Media LLC
Authors: William A. Nyberg; Pierre-Louis Bernard; Wayne Ngo; Charlotte H. Wang; Jonathan Ark; Allison Rothrock; Gina M. Borgo; Gabriella R. Kimmerly; Jae Hyung Jung; Vincent Allain; Jennifer R. Hamilton; Alisha Baldwin; Robert Stickels; Sarah Wyman; Safwaan H. Khan; Shanshan Lang; Donna Marsh; Niran Almudhfar; Catherine Novick; Yasaman Mortazavi; Shimin Zhang; Mahmoud M. AbdElwakil; Luis R. Sandoval; Sidney Hwang; Simon N. Chu; Hyuncheol Jung; Chang Liu; Devesh Sharma; Travis McCreary; Zhongmei Li; Ansuman T. Satpathy; Julia Carnevale; Rachel L. Rutishauser; M. Kyle Cromer; Kole T. Roybal; Stacie E. Dodgson; Jennifer A. Doudna; Aravind Asokan; Justin Eyquem