Interfacing Biomaterials with Synthetic T Cell Immunity

Abstract

The clinical success of cancer immunotherapy is providing exciting opportunities for the development of new methods to detect and treat cancer more effectively. A new generation of biomaterials is being developed to interface with molecular and cellular features of immunity and ultimately shape or control anti‐tumor responses. Recent advances that are supporting the advancement of engineered T cells are focused here. This class of cancer therapy has the potential to cure disease in subsets of patients, yet there remain challenges such as the need to improve response rates and safety while lowering costs to expand their use. To provide a focused overview, recent strategies in three areas of biomaterials research are highlighted: low‐cost cell manufacturing to broaden patient access, noninvasive diagnostics for predictive monitoring of immune responses, and strategies for in vivo control that enhance anti‐tumor immunity. These research efforts shed light on some of the challenges associated with T cell immunotherapy and how engineered biomaterials that interface with synthetic immunity are gaining traction to solve these challenges.

In vivo gene delivery to immune cells

“…For instance, using LVVs or retroviral vectors (RVV) to genetically modify autologous T cells with tumor-reactive chimeric antigen receptors (so called CAR T cells) has shown unprecedented therapeutic efficacy against hematological malignancies, as exemplified by the current FDA-approved products on the market [6]. Delivering genes to immune cells can be performed either ex vivo using cells harvested from a patient prior to re-infusion of the genetically modified cells back to the patient, or directly in the body (i.e., in vivo) [7]. In this review, we focus on in vivo gene delivery to immune cells, as it has the potential to bypass the complex logistics and high costs associated with an ex vivo manufacturing pipeline and to increase the functionality of the cell product [8,9].…”

In vivo mRNA delivery to virus-specific T cells by light-induced ligand exchange of MHC class I antigen-presenting nanoparticles

“…Recent studies include delivery of immunomodulatory molecules (e.g., transforming growth factor- inhibitors) using nano particles decorated with antibodies against T cell surface markers, including CD3 and programmed cell death protein1 (PD1), to en hance effector functions within the tumor microenvironment (1)(2)(3)(4). Programming endogenous CD3 + or CD8 + T cells with polymer/lipid nanoparticles (LNPs) loaded with nucleic acids [e.g., CD45 small interfering RNA (siRNA) and chimeric Ag receptor (CAR)-encoded DNA] has shown potential to silence target genes in T cells or for in situ manufacturing of CAR T cells (5)(6)(7)(8)(9). The ability to target Agspecific T cells offers opportunities to selectively augment diseaserelevant T cell subsets (e.g., viral or tumor Agspecific T cells) in vivo while maintaining homeostasis and selftolerance of the immune system (10).…”