Lipid nanoparticles for engineering next generation CAR T cell immunotherapy

Abstract

Lipid nanoparticles are a burgeoning technology which has vast potential to improve chimeric antigen receptor (CAR) T cell immunotherapy. This focused review provides an overview of CAR T cell therapy – highlighting its promises, limitations, and challenges – and describes ways in which lipid nanoparticles (LNPs) can be rationally designed to circumvent some of the challenges. Of particular note are antigen presenting cell-mimetic LNPs, which have the potential to streamline the CAR T cell production process by activating T cells and delivering the CAR transgene in a single step. Although the current clinical standard is ex vivo CAR T cell production, in vivo CAR T cell production represents a potentially transformative alternative. Recent innovations in each production method are described, with a particular emphasis on ways in which LNPs may enable in vivo CAR T cell production. The review concludes with a discussion of safety, immunogenicity, scalability, manufacturing, and regulatory factors which will be essential as LNP-based CAR T cell immunotherapies move toward clinical translation.