Nanoparticle-based immunotherapy of pancreatic cancer

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.

Advancing Cancer Treatment Through Nanotechnology Driven Immunotherapy for Pancreatic Cancer

“…Several reports have shown that a specific DC immature subset expands Tregs while suppressing CD8+ T cells to create an immunosuppressive microenvironment favorable for metastasis development. In addition, tumor infiltration of Treg cells plays a role in immune modulation by activating tumor-associated dendritic cells …”

“…In addition, tumor infiltration of Treg cells plays a role in immune modulation by activating tumor-associated dendritic cells. 5 B cells, or B lymphocytes, can also regulate the outcome of immunotherapies for PDAC. 83 B cells secrete IL-35, which prompts CD8+ T lymphocytes to activate the transcription factor STAT3.…”

“…The inadequacies of conventional model systems in replicating PDAC’s complex characteristics hinder effective treatment development, creating a gap between promising preclinical results and disappointing clinical outcomes. The intricate immunosuppressive tumor microenvironment further shields PDAC from effective immune responses. , However, nanotechnology offers promising solutions through targeted drug delivery and immune cell activation . This review highlights the design strategies of nanosystems, analyses advances in nanotechnology-driven immunotherapies, mainly through the integration of nanomaterials, examines potential delivery routes, and provides an overview of ongoing clinical trials exploring nanotherapeutics.…”

“…Nanotechnology can bring a paradigm shift in this scenario to overcome some of the challenges and enhance the effectiveness of immunotherapy . One potential possibility could be creating nanoparticles that specifically target either immune cells or cancer cells in tumors.…”

“…4,9 However, nanotechnology offers promising solutions through targeted drug delivery and immune cell activation. 5 This review highlights the design strategies of nanosystems, analyses advances in nanotechnology-driven immunotherapies, mainly through the integration of nanomaterials, examines potential delivery routes, and provides an overview of ongoing clinical trials exploring nanotherapeutics. By adopting nanotechnological strategies, we believe a paradigm shift in PDAC therapeutic management can be achieved for significantly reducing mortality rates.…”