Immune Netw.  2016 Feb;16(1):33-43. 10.4110/in.2016.16.1.33.

Use of Cell-Penetrating Peptides in Dendritic Cell-Based Vaccination

• Lim S
• Koo JH
• Choi JM

• KMID: 2154809
• DOI: http://doi.org/10.4110/in.2016.16.1.33

Abstract

Cell-penetrating peptides (CPPs) are short amino acids that have been widely used to deliver macromolecules such as proteins, peptides, DNA, or RNA, to control cellular behavior for therapeutic purposes. CPPs have been used to treat immunological diseases through the delivery of immune modulatory molecules in vivo. Their intracellular delivery efficiency is highly synergistic with the cellular characteristics of the dendritic cells (DCs), which actively uptake foreign antigens. DC-based vaccines are primarily generated by pulsing DCs ex vivo with various immunomodulatory antigens. CPP conjugation to antigens would increase DC uptake as well as antigen processing and presentation on both MHC class II and MHC class I molecules, leading to antigen specific CD4+ and CD8+ T cell responses. CPP-antigen based DC vaccination is considered a promising tool for cancer immunotherapy due to the enhanced CTL response. In this review, we discuss the various applications of CPPs in immune modulation and DC vaccination, and highlight the advantages and limitations of the current CPP-based DC vaccination.

Keyword

Cell-penetrating peptide; Dendritic cell; Vaccination; Immune modulation

MeSH Terms

Amino Acids
Antigen Presentation
Cell-Penetrating Peptides*
Dendritic Cells
DNA
Immune System Diseases
Immunotherapy
Peptides
RNA
Vaccination*
Vaccines
Amino Acids
Cell-Penetrating Peptides
DNA
Peptides
RNA
Vaccines

Figure

• 

  Figure 1 The mechanism of dendritic cell-based vaccination using cell-penetrating peptides. Dendritic cells can uptake CPP-antigens more efficiently than free-antigens. CPP-antigen can interact with the surface of dendritic cells through negatively charged glycosaminoclycans (GAGs), which can induce micropinocytosis or other endocytic pathways (①). Both CPP-antigens and free-antigens can also be localized into the cytoplasm via micropinocytosis by DCs (①). CPP antigens can escape endosomes because of their unique characteristics (②), while free-antigens have relatively low opportunity for endosomal escape (③). Antigens remaining in the endosomes are then subjected to lysosomal degradation (④) and presented on MHC class II molecules (⑤). Escaped antigens are degraded through the proteasome (⑥) and can be transported into vesicles containing MHC class I via TAP2 (⑦) or the endoplasmic reticulum (ER) through TAP1 (⑧). In the ER-Golgi pathway, degraded antigens are loaded on the MHC class I (⑨), and this MHC class I-antigen complex is presented on the surface of dendritic cells (⑩,⑪).

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