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

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• 作者：Fanny Coumes ; Chiung-Yi Huang ; Chung-Hsiung Huang ; Jean Coudane ; Dominique Domurado ; Suming Li ; Vincent Darcos ; Ming-Hsi Huang
• 刊名：Biomacromolecules
• 出版年：2015
• 出版时间：November 9, 2015
• 年：2015
• 卷：16
• 期：11
• 页码：3666-3673
• 全文大小：545K
• ISSN：1526-4602

文摘

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鈥揚EG-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鈥揚EG-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.