Science Spotlight: Using HIV to help allogeneic CAR T cells evade immune attack
BioCentury’s roundup of translational innovations also includes a human hypothalamus atlas from Novo and collaborators, and four papers with links to newcos
A group led by Michel Sadelain at Memorial Sloan Kettering Cancer Center devised a method to reduce immune rejection of allogeneic CAR T cells, borrowing from a mechanism that viruses use to evade the immune system. The modification could help allogeneic cells overcome their durability limitations in vivo.
CAR T cells with full human leukocyte antigen I (HLA-I) activity are rejected by host CD8+ T cells and NK cells. Eliminating HLA-I activity can avoid T cell recognition, but the cells are still susceptible to rejection by NK cells, which target cells missing HLA-I. The authors of the Nature paper showed that adding the HIV-1 viral immune evasion protein Nef to CAR T cells reduced HLA-I levels to a “happy medium,” leading to partial protection from CD8+ T cell killing without triggering NK cells...