Engineered Bacterial Biomaterials for Augmenting Adoptive Immune Cell Therapy Against Solid Tumors

Abstract

ABSTRACT Adoptive immune cell therapy (ACT) represents one of the most promising strategies in cancer immunotherapy, leveraging genetically engineered immune cells to recognize and eradicate tumor cells with high specificity. Durable remissions have been achieved in hematological malignancies, particularly with CD19‐targeted chimeric antigen receptor T (CAR‐T) cell therapies. However, the efficacy of ACT in solid tumors remains limited due to the immunosuppressive tumor microenvironment, tumor heterogeneity, and poor infiltration and persistence of the effector cells within tumor sites. Bacterial biomaterials, encompassing live bacteria and their acellular platforms, for example, outer membrane vesicles, represent emerging classes of programmable systems capable of reshaping the tumor immune microenvironment. In this review, we briefly illustrate the underlying molecular mechanisms by which bacterial biomaterials remodel the tumor environment and underscore the advances in the use of engineered bacterial biomaterials to enhance the efficacy of ACT in solid tumors, highlighting the underlying basic principles and engineering strategies to augment current adoptive cellular therapies for overcoming their faced dilemmas in solid tumor settings.