Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG-PLA Conjugate for Tuning Immunity

Biomacromolecules. 2015 Nov 9;16(11):3666-73. doi: 10.1021/acs.biomac.5b01150. Epub 2015 Oct 28.

Abstract

Cancer vaccines are considered to be a promising tool for cancer immunotherapy. However, a well-designed cancer vaccine should combine a tumor-associated antigen (TAA) with the most effective immunomodulatory agents and/or delivery system to provoke intense immune responses against the TAA. In the present study, we introduced a new approach by conjugating the immunomodulatory molecule LD-indolicidin to the hydrophilic chain end of the polymeric emulsifier poly(ethylene glycol)-polylactide (PEG-PLA), allowing the molecule to be located close to the surface of the resulting emulsion. A peptide/polymer conjugate, named LD-indolicidin-PEG-PLA, was synthesized by conjugation of the amine end-group of LD-indolicidin to the N-hydroxysuccinimide-activated carboxyl end-group of PEG. As an adjuvant for cancer immunotherapeutic use, TAA vaccine candidate formulated with the LD-indolicidin-PEG-PLA-stabilized squalene-in-water emulsion could effectively help to elicit a T helper (Th)1-dominant antigen-specific immune response as well as antitumor ability, using ovalbumin (OVA) protein/EG7 cells as a TAA/tumor cell model. Taken together, these results open up a new approach to the development of immunomodulatory antigen delivery systems for vaccine adjuvants and cancer immunotherapy technologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology*
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology
  • Drug Delivery Systems*
  • Emulsions
  • Female
  • Immunity / drug effects*
  • Immunomodulation
  • Immunotherapy
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Ovalbumin / chemistry
  • Peptides / chemistry*
  • Polyethylene Glycols / chemistry*
  • Squalene / chemistry
  • Succinimides / chemistry

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Antimicrobial Cationic Peptides
  • Antineoplastic Agents
  • Biocompatible Materials
  • Cancer Vaccines
  • Emulsions
  • Peptides
  • Succinimides
  • monomethoxypolyethyleneglycol-polylactide block copolymer
  • indolicidin
  • Polyethylene Glycols
  • Squalene
  • Ovalbumin
  • N-hydroxysuccinimide