Nucleus, GVHD, Science Highlights
AAV-P2X7 nanobody therapy for graft-versus-host disease
Elhage A, Hadaya JH, Sligar C, et al. Adeno-Associated Viral Vectors Encoding Anti-P2X7 Nanobodies Reduce Graft-Versus-Host Disease in a Humanized Mouse Model. Clinical & Translational Immunology. 2025; 14 (11) (doi: 10.1002/cti2.70061).
Preclinical evidence warrants further testing of P2X7 blockades as a preventative therapy against graft-versus-host disease (GVHD), a complication of allogeneic hematopoietic stem cell transplantation. The ligand-gated cation channel P2X7, expressed on immune cells, is associated with pro-inflammatory activity and is implicated in the development and advancement of GVHD and other inflammation-driven disorders. Previous research demonstrated that P2X7 blockade with small molecule inhibitors works against GVHD in a humanized murine model. Building on that discovery, scientists explored whether adeno-associated viral vectors encoding anti-mouse P2X7 nanobodies or both anti-mouse and anti-human P2X7 nanobodies have a similar effect on GVHD. The findings indicate that both types of nanobodies, but especially those that block both mouse and human P2X7, curtailed clinical and histological GVHD and shortened time to disease onset in humanized lab subjects, primarily due to a reduction in liver human T helper 17 cells.