Biomaterials of different sizes for enhanced adoptive cell transfer therapy in solid tumors.

Abstract

Adoptive cell therapy (ACT) shows significant efficacy against hema-tological malignancies but is limited in solid tumors by poor T-cell infiltration, immu-nosuppressive microenvironments, and systemic toxicity. Biomaterials spanning nano- to macroscales-including nanoparticles (NPs), microspheres/microneedles, and hydrogels-offer unique advantages for ex vivo cell engineering, in vivo delivery, and tumor micro-environment modulation. Specifically, NPs enable gene delivery, artificial antigen-pre-senting cell (aAPC) engineering, and immune microenvironment remodeling. Microspheres/microneedles improve immune cell expansion, targeted activation, and localized retention. Hydrogels enhance ACT via in situ genetic engineering, 3D culture support, and cytokine co-delivery. This review summarizes advances in biomaterial-enhanced ACT, highlighting their potential to improve delivery efficiency, amplify antitumor responses, and reduce toxicity. These insights may accelerate the clinical translation of ACT for solid tumors.