Background Chimeric antigen receptor (CAR) T therapy has shown remarkable success in treating liquid tumours but current approved therapies rely on autologous T cells which are expensive, difficult to manufacture and not readily available for patients whose disease progress rapidly. The production of safe and effective allogeneic CAR-T cells is needed to increase accessibility of CAR-T therapy and broaden its application. The main approach to generate allogeneic CAR-T therapy is by disrupting T cell receptor (TCR) expression to minimize Graft-versus-Host Disease (GVHD) mediated through the TCR of donor cells against the recipient's major histocompatibility complex (MHC). However, the TCR disruption approach has shown limited persistence in vivo [1] and in clinical trials [2] unlike the long term durability of autologous CAR-T cells.Here, we propose a novel platform for allogeneic CAR-T therapy that retains the TCR but inhibits TCR signalling by knocking out the Lymphocyte-specific protein tyrosine kinase (LCK)a well-established kinase for proximal TCR activation. This builds on the discovery that our second generation CD28-CAR can be activated independently of LCK unlike the endogenous TCR.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.