Long term bone-targeted CAR T therapy against osteoporosis

Osteoporosis is the most common bone disease for people over the age of 50. Osteoporosis is the result of a long-lasting remodeling imbalance between bone formation and bone resorption with a net loss of bone mass and increased risk of fractures. While most of the treatments have limited efficiency and require repeated administrations, we aimed at developing a treatment modality that offers long-term maintenance of bone health.

CAR-T cells are T cells, genetically modified to express a chimeric receptor that recognizes a specific tumor associated protein related to a cancer cell and specifically kills the targeted cells. This FDA-approved cancer immunotherapy combines the cytolytic potential of T cells activated specifically upon antibody recognition.

This project relies on recent advances in the field of CAR-T but we aim at designing a CAR-T to target the bone tissue and specifically deliver bone effectors upon target recognition. In the scope of this project, we designed an inducible CAR T cell that constitutively expresses a CAR that recognizes bone cells. By design, activation of this CAR-T cell does not kill the target cell but rather conditionally induces the secretion of a bone therapeutic agent. At this stage, we show that T cells transduced with our CAR construct are activated in contact to bone cells.

If validated in vivo and clinically, this approach is expected to offer a treatment that is administered only once and acts similarly to a vaccine against osteoporosis.