Cancer Immunotherapy and Delivery System: An Update

Abstract

With an understanding of immunity in the tumor microenvironment, immunotherapy turns out to be a powerful tool in the clinic to treat many cancers. The strategies applied in cancer immunotherapy mainly include blockade of immune checkpoints, adoptive transfer of engineered cells, such as T cells, natural killer cells, and macrophages, cytokine therapy, cancer vaccines, and oncolytic virotherapy. Many factors, such as product price, off-target side effects, immunosuppressive tumor microenvironment, and cancer cell heterogeneity, affect the treatment efficacy of immunotherapies against cancers. In addition, some treatments, such as chimeric antigen receptor (CAR) T cell therapy, are more effective in treating patients with lymphoma, leukemia, and multiple myeloma rather than solid tumors. To improve the efficacy of targeted immunotherapy and reduce off-target effects, delivery systems for immunotherapies have been developed in past decades using tools such as nanoparticles, hydrogel matrix, and implantable scaffolds. This review first summarizes the currently common immunotherapies and their limitations. It then synopsizes the relative delivery systems that can be applied to improve treatment efficacy and minimize side effects. The challenges, frontiers, and prospects for applying these delivery systems in cancer immunotherapy are also discussed. Finally, the application of these approaches in clinical trials is reviewed.

Keywords: T cell therapy; biomaterials; cancer immunotherapy; clinical application; delivery systems; intratumoral delivery; nanoparticles.

Figure 1

Different types of cancer immunotherapy. They mainly consist of blockade of immune checkpoints (e.g., antibody), adoptive transfer of engineered cells (e.g., chimeric antigen receptor (CAR) T cells, natural killer/NK cells, and macrophages), cytokine therapy, infection of oncolytic viruses, and cancer vaccines. Most of these therapeutics are administered by intravenous injection (i.v.), and some drugs are given by subcutaneous (s.c.), intraperitoneal (i.p.), or intramuscular (i.m.) injections.

Figure 2

Some representative formats of immunotherapy delivery systems. Nanoparticles (NPs) can be formed by different materials, including iron (e.g., gold), lipid, polymeric, and self-formatting NPs.