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Review
. 2022 Aug 29:9:948898.
doi: 10.3389/fmolb.2022.948898. eCollection 2022.

Nanoparticle-based immunotherapy of pancreatic cancer

Gaetan Aime Noubissi Nzeteu  1 , Bernhard F Gibbs  2 , Nika Kotnik  2 , Achim Troja  1 , Maximilian Bockhorn  1 , N Helge Meyer  1
Affiliations
Review

Nanoparticle-based immunotherapy of pancreatic cancer

Gaetan Aime Noubissi Nzeteu et al. Front Mol Biosci. .

Abstract

Pancreatic cancer (PC) has a complex and unique tumor microenvironment (TME). Due to the physical barrier formed by the desmoplastic stroma, the delivery of drugs to the tumor tissue is limited. The TME also contributes to resistance to various immunotherapies such as cancer vaccines, chimeric antigen receptor T cell therapy and immune checkpoint inhibitors. Overcoming and/or modulating the TME is therefore one of the greatest challenges in developing new therapeutic strategies for PC. Nanoparticles have been successfully used as drug carriers and delivery systems in cancer therapy. Recent experimental and engineering developments in nanotechnology have resulted in increased drug delivery and improved immunotherapy for PC. In this review we discuss and analyze the current nanoparticle-based immunotherapy approaches that are at the verge of clinical application. Particularly, we focus on nanoparticle-based delivery systems that improve the effectiveness of PC immunotherapy. We also highlight current clinical research that will help to develop new therapeutic strategies for PC and especially targeted immunotherapies based on immune checkpoint inhibitors.

Keywords: immune checkpoint inhibitors; immunotherapy; nanoparticles; pancreatic cancer; tumor microenvironment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of various immune checkpoint receptors and their respective ligands. Immune checkpoint molecules expressed on T cells bind to their respective ligands on APCs and/or tumor cells and trigger a negative or positive signal to T cells.
FIGURE 2
FIGURE 2
Schematic representation of active and passive targeting mechanisms. Active targeting is based on the presence of antibodies on the surface of the NP. In passive targeting, NPs mainly diffuse through leaky blood vessels and accumulate in the tumor tissue due to the EPR effect, while active targeting promotes the accumulation of NPs in the immediate vicinity of tumor cells. Formation of an antibody-antigen complex on the surface of cancer cells greatly facilitates endocytosis of the nanoparticles.
FIGURE 3
FIGURE 3
Schematic representation of NP strategies used to overcome and remodulate the TME or reactivate antitumor T cell activities in PC.
See this image and copyright information in PMC

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