Abstract
Traditional tumor vaccination approaches mostly focus on activating dendritic cells (DCs) by providing them with a source of tumor antigens and/or adjuvants, which in turn activate tumor-reactive T cells. Novel biomaterial-based cancer immunotherapeutic strategies focus on directly activating and stimulating T cells through molecular cues presented on synthetic constructs with the aim of improving T cell survival, more precisely steer T cell activation and direct T cell differentiation. Synthetic artificial antigen presenting cells (aAPCs) decorated with T cell-activating ligands are being developed to induce robust tumor-specific T cell responses, essentially bypassing DCs. In this perspective, we approach these promising new technologies from an immunological angle, first by identifying the CD4(+) and CD8(+) T cell subtypes that are imperative for robust anti-cancer immunity and subsequently discussing the molecular cues needed to induce these cells types. We will elaborate on how biomaterials can be applied to stimulate T cells in vitro and in vivo to improve their survival, activation and function. Scaffold-based methods can also be used as delivery vehicles for adoptive transfer of T cells, including tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor expressing (CAR) T cells, while simultaneously stimulating these cells. Finally, we provide suggestions on how these insights could advance the field of biomaterial-based activation and expansion of tumor-specific T cells in the future.