Abstract
Cationic nanoparticles have been shown to be surprisingly effective as cancer vaccine vehicles in preclinical and clinical studies. Cationic nanoparticles deliver tumor-associated antigens to dendritic cells and induce immune activation, resulting in strong antigen-specific cellular immune responses, as shown for a wide variety of vaccine candidates. In this review, we discuss the relation between the cationic nature of nanoparticles and the efficacy of cancer immunotherapy. Multiple types of lipid- and polymer-based cationic nanoparticulate cancer vaccines with various antigen types (e.g., mRNA, DNA, peptides and proteins) and adjuvants are described. Furthermore, we focus on the types of cationic nanoparticles used for T-cell induction, especially in the context of therapeutic cancer vaccination. We discuss different cationic nanoparticulate vaccines, molecular mechanisms of adjuvanticity and biodistribution profiles upon administration via different routes. Finally, we discuss the perspectives of cationic nanoparticulate vaccines for improving immunotherapy of cancer.
Highlights
Viral oncoproteins are only present in malignancies triggered by oncoviral infections, such as those caused by hepatitis B virus, human papillomavirus (HPV) and the Epstein-Barr virus (EBV)
S.c. injection of mRNA-loaded lipoplexes induced lower levels of antigen-specific T-cells compared to the i.v. injection. These results indicate that a short burst exposure via i.v. administration is the most efficient administration route for T-cell induction for mRNA-based nanoparticulate cancer vaccines
Cationic nanoparticulate cancer vaccine formulations are very promising platforms for specific immunotherapy of cancer. Such nanoparticulate formulations can be used in synthetically produced antigens as multi-epitope vaccines and readily produced under cGMP conditions
Summary
For direct in vivo vaccination approaches, a large variety of delivery vehicles and adjuvants have been developed and investigated in combination with a multitude of tumor antigens Despite these efforts, it has proven to be difficult to induce high numbers of functional tumorspecific T-cells in cancer patients [9,20,25]. A large number of nanoparticle types have been developed to target DCs and induce cellular immune responses Among these nanoparticles, cationic particles are of special interest, because they have shown to have superior immunostimulatory properties as compared to their neutral and anionic analogues and have proven to be potent inducers of antigen-specific Tcells [9,26,27,28,29,30,31,32,33,34,35]. We discuss several molecular mechanisms via which cationic nanoparticles can enhance the efficacy of cancer vaccines
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