Interfacial T cell engineering

Therapeutic T cell products and immunotherapies that target T cells require the manipulation of T cells ex vivo or in situ. Endogenous T cell functions are guided by their physical and biological interactions with other cells and tissues, occurring at the T cell membrane. Such T cell interfaces can be recapitulated using nanotechnologies and microtechnologies to precisely modulate and control T cell function. In this Review, we first discuss the structural and biochemical features of T cell interfaces at the cell and tissue levels, outlining how these interfaces dictate T cell function and fate. We then examine how T cell interfaces can be engineered at the nanoscale and microscale to create models for mechanistic studies, as well as scalable platforms for identifying, engineering, screening and sorting therapeutic T cells. Finally, we highlight key challenges and opportunities in the scaling and translation of these platforms for their integration into T cell therapy manufacturing processes. The function and fate of T cells are dictated by their various dynamic interactions with cells and tissues. This Review discusses the recreation of key T cell interfaces using nanotechnologies and microtechnologies for the mechanistic study of T cell biology, as well as the manufacturing and sorting of T cell products.