Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine

Abstract

The aim of this research was to develop a targeted antigen–adjuvant assembled delivery system that will enable dendritic cells (DCs) to efficiently mature to recognize antigens released from tumor cells. It is important to target the DCs with greater efficiency to prime T cell immune responses. In brief, model antigen, ovalbumin (OV), and monophosphoryl lipid A adjuvant were encapsulated within the nanoparticle (NP) by double emulsification solvent evaporation method. Targeted NPs were obtained through ligand incorporation via physical adsorption or chemical conjugation process. Intracellular uptake of the NPs and the maturation of DCs were evaluated with flow cytometry. Remarkably, the developed delivery system had suitable physicochemical properties, such as particle size, surface charge, OV encapsulation efficiency, biphasic OV release pattern, and safety profile. The ligand modified formulations had higher targeting efficiency than the non-tailored NPs. This was also evident when the targeted formulations expressed comparatively higher fold increase in surface activation markers such as CD40, CD86, and major histocompatibility complex class II molecules. The maturation of DCs was further confirmed through secretion of extracellular cytokines compared to control cells in the DC microenvironment. Physicochemical characterization of NPs was performed based on the polymer end groups, their viscosities, and ligand-NP bonding type. In conclusion, the DC stimulatory response was integrated to develop a relationship between the NP structure and desired immune response. Therefore, the present study narrates a comparative evaluation of some selected parameters to choose a suitable formulation useful for in vivo cancer immunotherapy.

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

“…As is well known, DCs, the most powerful APCs, initiate and regulate humoral and cellular immune responses, so target delivery to DCs can be achieved by conjugating targeting ligands onto the surface of antigen‐loaded nanoparticles. These ligands specifically bind to the surface receptors expressed by DCs, such as mannose, DEC‐205, CD40, CD11c, and DC‐SIGN receptors . Such delivery systems have indeed enhanced DCs engulfment in comparison to their nontarget counterparts.…”

Pru p 3‐Glycodendropeptides Based on Mannoses Promote Changes in the Immunological Properties of Dendritic and T‐Cells from LTP‐Allergic Patients

“…CLRs are pattern recognition receptors expressed on the surface of DCs that are characterized by a carbohydrate recognition domain that interacts with mannose or fucose in a calcium‐dependent manner . Their engagement not only mediates endocytosis but can modulate the Th1/Treg response, critical for tolerance induction during immunotherapy, as well as antitumor and antiviral therapy . The main CLRs expressed by DCs that recognize sugars are: the mannose receptor (MR; CD206), dendritic‐cell‐specific intercellular adhesion molecule 3‐grabbing nonintegrin (DC‐SIGN; CD209), and Dectin‐2.…”

Biodegradable polymers for modern vaccine development

“…The cellular uptake of nano-and micro-sized PLGA particles is well documented [43]; these PLGA particles can protect Ag from premature proteolytic degradation and can function in vaccine delivery [44]. We, and others, have investigated various surface engineering strategies to overcome these problems [47][48][49][50] PLGA biopolymers have considerable flexibility in terms of surface modification or functionalization for targeting [38,44]. However, the clinical development of PLGA-NPs presents several challenges, including their synthetic hydrophobic surface, low transfection efficiency (for DNA vaccines), short circulation half-life, and nonspecific tissue distribution.…”