Prospects for the Use of Metal-Based Nanoparticles as Adjuvants for Local Cancer Immunotherapy

Abstract

Immunotherapy is among the most effective approaches for treating cancer. One of the key aspects for successful immunotherapy is to achieve a strong and stable antitumor immune response. Modern immune checkpoint therapy demonstrates that cancer can be defeated. However, it also points out the weaknesses of immunotherapy, as not all tumors respond to therapy and the co-administration of different immunomodulators may be severely limited due to their systemic toxicity. Nevertheless, there is an established way through which to increase the immunogenicity of immunotherapy-by the use of adjuvants. These enhance the immune response without inducing such severe adverse effects. One of the most well-known and studied adjuvant strategies to improve immunotherapy efficacy is the use of metal-based compounds, in more modern implementation-metal-based nanoparticles (MNPs), which are exogenous agents that act as danger signals. Adding innate immune activation to the main action of an immunomodulator makes it capable of eliciting a robust anti-cancer immune response. The use of an adjuvant has the peculiarity of a local administration of the drug, which positively affects its safety. In this review, we will consider the use of MNPs as low-toxicity adjuvants for cancer immunotherapy, which could provide an abscopal effect when administered locally.

Keywords: adjuvant; cancer immunotherapy; local administration; metal-based nanoparticles.

Figure 1

Augmented cancer–immunity cycle. The classic activation, through MHCI-CD8-acivated T cells, is on the upper side. The MHCII-CD4-NK axis is at the bottom. Ag—antigen, Ab—antibody, TCR—T cell receptor, and FcγIIIa—low affinity immunoglobulin gamma Fc region receptor III-A (CD16a).

Figure 2

Clinical trials limited to “immunotherapy Intratumoral/Cancer”. An approximate distribution by type of therapy is given. See text for detailed explanations and limitations.

Figure 3

Possible applications of ferrum-based NPs. Fe—a ferrum-based NP and AG—antigen.

Figure 4

Possible mechanism of the triggered immune cells and the immune response amplification via the K+ mediated-inflammasome activation by functionalized TiO₂ nanoparticles.

Figure 5

Mn²⁺ as an activator of the cGAS-STING pathway. Abbreviations: cGAS—cGAMP synthase; IFI16—interferon γ-inducible protein 16; DDX41—helicase DEAD box polypeptide 41; c-di-GMP—cyclic di-GMP; c-di-AMP—cyclic di-AMP; STING—stimulator of interferon genes; IRF3—interferon (IFN) regulatory factor 3; TBK1—TANK-binding kinase 1; cGAMP—cyclic guanosine monophosphate-adenosine monophosphate; DAI—DNA-dependent activator of IRFs; IFNs—type-I interferons; STING (also known as MITA, MPYS, or ERIS); cGAMP—cyclic GMP-AMP; and IRF3—IFN-regulatory factor 3.