Biomaterial-Enabled In vivo T Cell Engineering: A New Paradigm for Cell Therapy.

T cell therapies have transformed treatment for previously intractable diseases. However, their full potential remains constrained by reliance on ex vivo cell manipulations, which reduces cell quality, drives up manufacturing costs, and requires lengthy production times, ultimately reducing treatment efficacy and restricting patient access. Recent breakthroughs in biomaterials science, immunoengineering, and genetic editing have catalyzed a paradigm shift toward direct in vivo immune cell engineering using instructive biomaterials. These emerging strategies circumvent traditional limitations by dramatically reducing costs, eliminating manufacturing delays, and improving therapeutic outcomes through preservation of native cell states and functions. Key technological advances include highly specific targeted biomaterial-assisted gene delivery and instructive biomaterials that establish controlled microenvironments for precise immune cell programming and modulation. In this Perspective, we examine how biomaterials are redefining T cell therapies across a range of pathological contexts, from cancer to autoimmune disease. We analyze emerging breakthrough platforms, highlight their therapeutic potential, and discuss key challenges limiting clinical adoption. Looking ahead, we provide insights into future developments that could democratize access to these transformative immunotherapies.