Glycoconjugate Nanoparticle-Based Systems in Cancer Immunotherapy: Novel Designs and Recent Updates

Abstract

For many years, cell-surface glycans (in particular, Tumor-Associated Carbohydrate Antigens, TACAs) have been the target of both passive and active anticancer immunotherapeutic design. Recent advances in immunotherapy as a treatment for a variety of malignancies has revolutionized anti-tumor treatment regimens. Checkpoint inhibitors, Chimeric Antigen Receptor T-cells, Oncolytic virus therapy, monoclonal antibodies and vaccines have been developed and many approvals have led to remarkable outcomes in a subset of patients. However, many of these therapies are very selective for specific patient populations and hence the search for improved therapeutics and refinement of techniques for delivery are ongoing and fervent research areas. Most of these agents are directed at protein/peptide epitopes, but glycans–based targets are gaining in popularity, and a handful of approved immunotherapies owe their activity to oligosaccharide targets. In addition, nanotechnology and nanoparticle-derived systems can help improve the delivery of these agents to specific organs and cell types based on tumor-selective approaches. This review will first outline some of the historical beginnings of this research area and subsequently concentrate on the last 5 years of work. Based on the progress in therapeutic design, predictions can be made as to what the future holds for increasing the percentage of positive patient outcomes for optimized systems.

Carrier diversity and chemical ligations in the toolbox for designing tumor-associated carbohydrate antigens (TACAs) as synthetic vaccine candidates

“…A thorough analysis by Barchi Jr. describing glycoconjugate-based nanomaterials as they apply to cancer immunotherapy has been freshly published. 224 Besides liposomal formulations, the author also describes the use of hydrogel, Scheme 24 TACA-based VLPs vaccines using Qb carrier. 223 polymeric materials, and gold nanomaterials, an avenue initially and successfully exploited by his group with the TF antigen.…”

Pairing Nanoparticles Geometry with TLR Agonists to Modulate Immune Responses for Vaccine Development

“…The importance of nanotechnology in vaccine development remains a powerful impetus for exploring new conceptual changes in nanostructures to generate an easy and efficient platform for developing antibodies against poor immunogenic antigens such as tumor-associated carbohydrate antigens (TACAs). − Among various nanostructures, gold nanoparticles have attracted strong interest due to their facile synthetic methods, surface functionalization, and nonimmunogenic and nontoxic nature. − Gold nanoparticle-based vaccine approaches frequently rely on decorating antigens and adjuvant molecules on nanoparticles and their access to immune cells and receptors. , Consequently, understanding the impact of the geometry of the nanoparticles, the local concentration of the ligands, and the spacers between the nanostructures and ligands influencing the immune responses is persistently considered. − However, a head-to-head comparison of more than one adjuvant on a similar nanostructure platform is required to develop a broad immune-modulatory nanotechnology platform. To expand our knowledge of nanotechnology-based vaccine development, we studied the synthesis of spherical, rod-, and star-shaped gold nanostructures appended with CpG and imidazoquinoline ligands to evaluate shape-dependent immune cell uptake and immune modulation.…”