In Situ Reprogramming of Immune Cells Using Synthetic Nanomaterials

In the past decade, adoptive cell therapy with chimeric antigen receptor-T (CAR-T) cells has revolutionized cancer treatment. However, the complexity and high costs involved in manufacturing current adoptive cell therapy greatly inhibit its widespread availability and access. To address this, in situ cell therapy, which directly reprograms immune cells inside the body, has recently been developed as a promising alternative. Here, an overview of the recent progress in the development of synthetic nanomaterials is provided to deliver plasmid DNA or mRNA for in situ reprogramming of T cells and macrophages, focusing especially on in situ CAR therapies. Also, the main challenges for in situ immune cell reprogramming are discussed and some approaches to overcome these barriers to fulfill the clinical applications are proposed.