Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG–PLA Conjugate for Tuning Immunity
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 p...
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| Veröffentlicht in: | Biomacromolecules 2015-11, Vol.16 (11), p.3666-3673 |
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| creator | Coumes, Fanny Huang, Chiung-Yi Huang, Chung-Hsiung Coudane, Jean Domurado, Dominique Li, Suming Darcos, Vincent Huang, Ming-Hsi |
| description | 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. |
| doi_str_mv | 10.1021/acs.biomac.5b01150 |
| format | Article |
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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. 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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.</description><subject>Adjuvants, Immunologic - chemistry</subject><subject>Adjuvants, Immunologic - pharmacology</subject><subject>Animals</subject><subject>Antigens, Neoplasm - chemistry</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Antimicrobial Cationic Peptides - chemistry</subject><subject>Antimicrobial Cationic Peptides - pharmacology</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biocompatible Materials - chemistry</subject><subject>Biocompatible Materials - pharmacology</subject><subject>Cancer Vaccines - chemistry</subject><subject>Cancer Vaccines - immunology</subject><subject>Chemical Sciences</subject><subject>Drug Delivery Systems</subject><subject>Emulsions</subject><subject>Female</subject><subject>Immunity - drug effects</subject><subject>Immunomodulation</subject><subject>Immunotherapy</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - immunology</subject><subject>Ovalbumin - chemistry</subject><subject>Peptides - chemistry</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Squalene - chemistry</subject><subject>Succinimides - chemistry</subject><issn>1525-7797</issn><issn>1526-4602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kctu2zAQRYkiRfNof6CLgMt0IYcPUZSWrvMEDNRA0zVBSSOHhki6ImXAQBf9h_5hviR05HQ1g4uDO7hzEfpKyYwSRq91E2a18VY3M1ETSgX5gM6oYEWWF4SdvO0ik7KSp-g8hA0hpOK5-IROWZFLzhk7Q39uIJi1w9q1-AZ20PutBRex7_CjtaPz1rdjr6Mf9njuolmDS1xvdpCEn_sQwQb8XQdosXd4BdtoWrhe3d6__P23Ws7xwrvNuNYRcOcH_DQ649aTs4n7z-hjp_sAX47zAv26u31aPGTLH_ePi_ky06zMY1blpNSi5XmRE6h11YEEBgJ02RWVbKRseMlpS1M8Jjoohex0QZuuFqQinLT8An2bfJ91r7aDsXrYK6-Nepgv1UEjtChLxsWOJvZqYreD_z1CiMqa0EDfawd-DIpKzng6VcqEXh7RsbbQ_nd-_24CZhOQmlIbPw4upVSUqEN96iBO9aljffwVWrSOQw</recordid><startdate>20151109</startdate><enddate>20151109</enddate><creator>Coumes, Fanny</creator><creator>Huang, Chiung-Yi</creator><creator>Huang, Chung-Hsiung</creator><creator>Coudane, Jean</creator><creator>Domurado, Dominique</creator><creator>Li, Suming</creator><creator>Darcos, Vincent</creator><creator>Huang, Ming-Hsi</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-3660-2313</orcidid><orcidid>https://orcid.org/0000-0002-3345-1479</orcidid><orcidid>https://orcid.org/0000-0003-0031-0984</orcidid><orcidid>https://orcid.org/0000-0002-1073-5882</orcidid></search><sort><creationdate>20151109</creationdate><title>Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG–PLA Conjugate for Tuning Immunity</title><author>Coumes, Fanny ; Huang, Chiung-Yi ; Huang, Chung-Hsiung ; Coudane, Jean ; Domurado, Dominique ; Li, Suming ; Darcos, Vincent ; Huang, Ming-Hsi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a284t-9408a5d34640eba9fe7e2e5ea8f697c77c3831d100925fe857fa61cfb509030d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adjuvants, Immunologic - chemistry</topic><topic>Adjuvants, Immunologic - pharmacology</topic><topic>Animals</topic><topic>Antigens, Neoplasm - chemistry</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Antimicrobial Cationic Peptides - chemistry</topic><topic>Antimicrobial Cationic Peptides - pharmacology</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biocompatible Materials - chemistry</topic><topic>Biocompatible Materials - pharmacology</topic><topic>Cancer Vaccines - chemistry</topic><topic>Cancer Vaccines - immunology</topic><topic>Chemical Sciences</topic><topic>Drug Delivery Systems</topic><topic>Emulsions</topic><topic>Female</topic><topic>Immunity - drug effects</topic><topic>Immunomodulation</topic><topic>Immunotherapy</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - immunology</topic><topic>Ovalbumin - chemistry</topic><topic>Peptides - chemistry</topic><topic>Polyethylene Glycols - chemistry</topic><topic>Squalene - chemistry</topic><topic>Succinimides - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coumes, Fanny</creatorcontrib><creatorcontrib>Huang, Chiung-Yi</creatorcontrib><creatorcontrib>Huang, Chung-Hsiung</creatorcontrib><creatorcontrib>Coudane, Jean</creatorcontrib><creatorcontrib>Domurado, Dominique</creatorcontrib><creatorcontrib>Li, Suming</creatorcontrib><creatorcontrib>Darcos, Vincent</creatorcontrib><creatorcontrib>Huang, Ming-Hsi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Biomacromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coumes, Fanny</au><au>Huang, Chiung-Yi</au><au>Huang, Chung-Hsiung</au><au>Coudane, Jean</au><au>Domurado, Dominique</au><au>Li, Suming</au><au>Darcos, Vincent</au><au>Huang, Ming-Hsi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG–PLA Conjugate for Tuning Immunity</atitle><jtitle>Biomacromolecules</jtitle><addtitle>Biomacromolecules</addtitle><date>2015-11-09</date><risdate>2015</risdate><volume>16</volume><issue>11</issue><spage>3666</spage><epage>3673</epage><pages>3666-3673</pages><issn>1525-7797</issn><eissn>1526-4602</eissn><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.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>26473322</pmid><doi>10.1021/acs.biomac.5b01150</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-3660-2313</orcidid><orcidid>https://orcid.org/0000-0002-3345-1479</orcidid><orcidid>https://orcid.org/0000-0003-0031-0984</orcidid><orcidid>https://orcid.org/0000-0002-1073-5882</orcidid></addata></record> |
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| subjects | 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 Chemical Sciences 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 |
| title | Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG–PLA Conjugate for Tuning Immunity |
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