Enhancing cancer immunotherapy through nanotechnology-mediated tumor infiltration and activation of immune cells

Abstract

Cancer immunotherapy has become arguably the most promising advancement in cancer research and therapy in recent years. The efficacy of cancer immunotherapy is critically dependent on specific physiological and physical processes - collectively referred to as transport barriers - including the activation of T cells by antigen presenting cells, T cells migration to and penetration into the tumor microenvironment, and movement of nutrients and other immune cells through the tumor microenvironment. Nanotechnology-based approaches have great potential to help overcome these transport barriers. In this review, we discuss the ways that nanotechnology is being leveraged to improve the efficacy and potency of various cancer immunotherapies.

Keywords: Cancer immunotherapy; Nanotechnology; Tumor microenvironment; Tumor-infiltrating lymphocytes.

Fig. 1

Nanotechnology-based immunotherapies overcome transport barriers to promote tissue infiltration of immune cells. Nanoparticles and microparticles can be loaded with multiple payloads, such as drugs, small molecules, oligonucleotides, immunomodulatory compounds, etc. These nanotechnologies can be directly injected into cancer patients as non-dendritic cell (DC) cancer vaccines, subsequently stimulating DCs in vivo and leading to the physical transport of DCs into lymph nodes for T-cell stimulation. Alternatively, these particles can be used to generate DC vaccines ex vivo for subsequent injection into cancer patients for T-cell stimulation. Nanotechnologies can also be applied to enhance T-cell expansion in vitro for subsequent adoptive T cell therapy, incorporated into adoptive T cell therapies to deliver potent anticancer therapeutics directly to tumor sites by tumor infiltration of T lymphocytes, indirectly remodel the tumor extracellular matrix (ECM), or directly target matricellular proteins.