Loading…
Liposomal Formulations of Synthetic MUC1 Peptides: Effects of Encapsulation versus Surface Display of Peptides on Immune Responses
Synthetic human MUC1 peptides are important candidates for therapeutic cancer vaccines. To explore whether a human MUC1 peptide BP25 (STAPPAHGVTSAPDTRPAPGSTAPP) can be rendered immunogenic by incorporation in liposomes, the effects of physical association of the peptide with liposomes on immune resp...
Saved in:
| Published in: | Bioconjugate chemistry 1998-07, Vol.9 (4), p.451-458 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-a414t-33697694ee6af19e565e751b7b2026843f900fcc71358deeeb105eb1f754e43b3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-a414t-33697694ee6af19e565e751b7b2026843f900fcc71358deeeb105eb1f754e43b3 |
| container_end_page | 458 |
| container_issue | 4 |
| container_start_page | 451 |
| container_title | Bioconjugate chemistry |
| container_volume | 9 |
| creator | Guan, Holly H Budzynski, Wladyslaw Koganty, R. Rao Krantz, Mark J Reddish, Mark A Rogers, James A Longenecker, B. Michael Samuel, John |
| description | Synthetic human MUC1 peptides are important candidates for therapeutic cancer vaccines. To explore whether a human MUC1 peptide BP25 (STAPPAHGVTSAPDTRPAPGSTAPP) can be rendered immunogenic by incorporation in liposomes, the effects of physical association of the peptide with liposomes on immune responses were investigated. Lipid conjugated and nonconjugated MUC1 peptides were incorporated in liposomes with a composition of distearoylphosphatidylcholine/cholesterol/dimyristoylphosphatidylglycerol (3:1:0.25, molar ratio) containing monophosphoryl lipid A (1% w/w of the total lipids). Liposomes were characterized for peptide retention by HPLC and for surface peptide display of MUC1 epitopes by flow cytometry. C57BL/6 mice were immunized with lipopeptide alone, peptide mixed with peptide-free liposomes, and peptide associated with liposomes in entrapped or surface-exposed forms. T cell proliferative responses, cytokine patterns, and antibody isotypes were studied. Results showed that immune responses were profoundly influenced by the liposome formulations. Physically associated, either encapsulated or surface-exposed, peptide liposomes elicited strong antigen-specific T cell responses, but not lipopeptide alone or peptide mixed with peptide-free liposomes. Analysis of the cytokines secreted by the proliferating T cells showed a high level of IFN-γ and undetectable levels of IL-4, indicating a T helper type 1 response. Thus, physical association of the peptide with liposomes was required for T cell proliferative responses, but the mode of association was not critical. On the other hand, the nature of the association significantly affected humoral immune responses. Only the surface-exposed peptide liposomes induced MUC1-specific antibodies. A domination of anti-MUC1 IgG2b over IgG1 (94 versus 6%) was observed. Our results support the hypothesis that different immune pathways are stimulated by different liposome formulations. This study demonstrated that a liposome delivery system could be tailored to induce either a preferential cellular or humoral immune response. |
| doi_str_mv | 10.1021/bc970183n |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_80008941</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>80008941</sourcerecordid><originalsourceid>FETCH-LOGICAL-a414t-33697694ee6af19e565e751b7b2026843f900fcc71358deeeb105eb1f754e43b3</originalsourceid><addsrcrecordid>eNptkM9uEzEQhy0EKqVw4AGQfAGJw4K99tprblWaQkUQVZMqR8vrjMWW_Ydnt2puvXDgNXkSXBJy4jIz0u-bGekj5CVn7zjL-fvKG814KbpH5JgXOctkyfPHaWZSZLxk-VPyDPGGMWZ4mR-RI6OUNlIdk5-Leuixb11Dz_vYTo0b675D2ge63HbjNxhrT79czzi9hGGsN4Afft__ovMQwI9_sXnn3YD7RXoLESekyykG54Ge1Tg0bvvA_dunibpo26kDegU4pGeAz8mT4BqEF_t-Qq7P56vZp2zx9ePF7HSROcnlmAmhjFZGAigXuIFCFaALXukqZ7kqpQiGseC95qIoNwBQcVakEnQhQYpKnJA3u7tD7H9MgKNta_TQNK6DfkJbJkOlkTyBb3egjz1ihGCHWLcubi1n9kG5PShP7Kv90alqYXMg945Tnu3yGke4O8QufrdKC13Y1eXSrq7Wn9VaLu068a93vPNob_opdknJf_7-ARDimW0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>80008941</pqid></control><display><type>article</type><title>Liposomal Formulations of Synthetic MUC1 Peptides: Effects of Encapsulation versus Surface Display of Peptides on Immune Responses</title><source>American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list)</source><creator>Guan, Holly H ; Budzynski, Wladyslaw ; Koganty, R. Rao ; Krantz, Mark J ; Reddish, Mark A ; Rogers, James A ; Longenecker, B. Michael ; Samuel, John</creator><creatorcontrib>Guan, Holly H ; Budzynski, Wladyslaw ; Koganty, R. Rao ; Krantz, Mark J ; Reddish, Mark A ; Rogers, James A ; Longenecker, B. Michael ; Samuel, John</creatorcontrib><description>Synthetic human MUC1 peptides are important candidates for therapeutic cancer vaccines. To explore whether a human MUC1 peptide BP25 (STAPPAHGVTSAPDTRPAPGSTAPP) can be rendered immunogenic by incorporation in liposomes, the effects of physical association of the peptide with liposomes on immune responses were investigated. Lipid conjugated and nonconjugated MUC1 peptides were incorporated in liposomes with a composition of distearoylphosphatidylcholine/cholesterol/dimyristoylphosphatidylglycerol (3:1:0.25, molar ratio) containing monophosphoryl lipid A (1% w/w of the total lipids). Liposomes were characterized for peptide retention by HPLC and for surface peptide display of MUC1 epitopes by flow cytometry. C57BL/6 mice were immunized with lipopeptide alone, peptide mixed with peptide-free liposomes, and peptide associated with liposomes in entrapped or surface-exposed forms. T cell proliferative responses, cytokine patterns, and antibody isotypes were studied. Results showed that immune responses were profoundly influenced by the liposome formulations. Physically associated, either encapsulated or surface-exposed, peptide liposomes elicited strong antigen-specific T cell responses, but not lipopeptide alone or peptide mixed with peptide-free liposomes. Analysis of the cytokines secreted by the proliferating T cells showed a high level of IFN-γ and undetectable levels of IL-4, indicating a T helper type 1 response. Thus, physical association of the peptide with liposomes was required for T cell proliferative responses, but the mode of association was not critical. On the other hand, the nature of the association significantly affected humoral immune responses. Only the surface-exposed peptide liposomes induced MUC1-specific antibodies. A domination of anti-MUC1 IgG2b over IgG1 (94 versus 6%) was observed. Our results support the hypothesis that different immune pathways are stimulated by different liposome formulations. This study demonstrated that a liposome delivery system could be tailored to induce either a preferential cellular or humoral immune response.</description><identifier>ISSN: 1043-1802</identifier><identifier>EISSN: 1520-4812</identifier><identifier>DOI: 10.1021/bc970183n</identifier><identifier>PMID: 9667946</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>AIDS/HIV ; Amino Acid Sequence ; Animals ; Antibodies, Monoclonal - immunology ; Antibody Formation - drug effects ; Antibody Specificity ; Chemistry, Pharmaceutical ; Cytokines - metabolism ; Drug Carriers ; Epitopes - analysis ; Female ; Humans ; Liposomes ; Lymphocyte Activation - drug effects ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mucin-1 - administration & dosage ; Mucin-1 - immunology ; Mucin-1 - pharmacology ; Peptide Fragments - administration & dosage ; Peptide Fragments - immunology ; Peptide Fragments - pharmacology ; Surface Properties ; T-Lymphocytes - drug effects ; T-Lymphocytes - immunology ; Th1 Cells - drug effects ; Th1 Cells - immunology ; Th1 Cells - metabolism</subject><ispartof>Bioconjugate chemistry, 1998-07, Vol.9 (4), p.451-458</ispartof><rights>Copyright © 1998 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a414t-33697694ee6af19e565e751b7b2026843f900fcc71358deeeb105eb1f754e43b3</citedby><cites>FETCH-LOGICAL-a414t-33697694ee6af19e565e751b7b2026843f900fcc71358deeeb105eb1f754e43b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9667946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guan, Holly H</creatorcontrib><creatorcontrib>Budzynski, Wladyslaw</creatorcontrib><creatorcontrib>Koganty, R. Rao</creatorcontrib><creatorcontrib>Krantz, Mark J</creatorcontrib><creatorcontrib>Reddish, Mark A</creatorcontrib><creatorcontrib>Rogers, James A</creatorcontrib><creatorcontrib>Longenecker, B. Michael</creatorcontrib><creatorcontrib>Samuel, John</creatorcontrib><title>Liposomal Formulations of Synthetic MUC1 Peptides: Effects of Encapsulation versus Surface Display of Peptides on Immune Responses</title><title>Bioconjugate chemistry</title><addtitle>Bioconjugate Chem</addtitle><description>Synthetic human MUC1 peptides are important candidates for therapeutic cancer vaccines. To explore whether a human MUC1 peptide BP25 (STAPPAHGVTSAPDTRPAPGSTAPP) can be rendered immunogenic by incorporation in liposomes, the effects of physical association of the peptide with liposomes on immune responses were investigated. Lipid conjugated and nonconjugated MUC1 peptides were incorporated in liposomes with a composition of distearoylphosphatidylcholine/cholesterol/dimyristoylphosphatidylglycerol (3:1:0.25, molar ratio) containing monophosphoryl lipid A (1% w/w of the total lipids). Liposomes were characterized for peptide retention by HPLC and for surface peptide display of MUC1 epitopes by flow cytometry. C57BL/6 mice were immunized with lipopeptide alone, peptide mixed with peptide-free liposomes, and peptide associated with liposomes in entrapped or surface-exposed forms. T cell proliferative responses, cytokine patterns, and antibody isotypes were studied. Results showed that immune responses were profoundly influenced by the liposome formulations. Physically associated, either encapsulated or surface-exposed, peptide liposomes elicited strong antigen-specific T cell responses, but not lipopeptide alone or peptide mixed with peptide-free liposomes. Analysis of the cytokines secreted by the proliferating T cells showed a high level of IFN-γ and undetectable levels of IL-4, indicating a T helper type 1 response. Thus, physical association of the peptide with liposomes was required for T cell proliferative responses, but the mode of association was not critical. On the other hand, the nature of the association significantly affected humoral immune responses. Only the surface-exposed peptide liposomes induced MUC1-specific antibodies. A domination of anti-MUC1 IgG2b over IgG1 (94 versus 6%) was observed. Our results support the hypothesis that different immune pathways are stimulated by different liposome formulations. This study demonstrated that a liposome delivery system could be tailored to induce either a preferential cellular or humoral immune response.</description><subject>AIDS/HIV</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibody Formation - drug effects</subject><subject>Antibody Specificity</subject><subject>Chemistry, Pharmaceutical</subject><subject>Cytokines - metabolism</subject><subject>Drug Carriers</subject><subject>Epitopes - analysis</subject><subject>Female</subject><subject>Humans</subject><subject>Liposomes</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Sequence Data</subject><subject>Mucin-1 - administration & dosage</subject><subject>Mucin-1 - immunology</subject><subject>Mucin-1 - pharmacology</subject><subject>Peptide Fragments - administration & dosage</subject><subject>Peptide Fragments - immunology</subject><subject>Peptide Fragments - pharmacology</subject><subject>Surface Properties</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - immunology</subject><subject>Th1 Cells - drug effects</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - metabolism</subject><issn>1043-1802</issn><issn>1520-4812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><recordid>eNptkM9uEzEQhy0EKqVw4AGQfAGJw4K99tprblWaQkUQVZMqR8vrjMWW_Ydnt2puvXDgNXkSXBJy4jIz0u-bGekj5CVn7zjL-fvKG814KbpH5JgXOctkyfPHaWZSZLxk-VPyDPGGMWZ4mR-RI6OUNlIdk5-Leuixb11Dz_vYTo0b675D2ge63HbjNxhrT79czzi9hGGsN4Afft__ovMQwI9_sXnn3YD7RXoLESekyykG54Ge1Tg0bvvA_dunibpo26kDegU4pGeAz8mT4BqEF_t-Qq7P56vZp2zx9ePF7HSROcnlmAmhjFZGAigXuIFCFaALXukqZ7kqpQiGseC95qIoNwBQcVakEnQhQYpKnJA3u7tD7H9MgKNta_TQNK6DfkJbJkOlkTyBb3egjz1ihGCHWLcubi1n9kG5PShP7Kv90alqYXMg945Tnu3yGke4O8QufrdKC13Y1eXSrq7Wn9VaLu068a93vPNob_opdknJf_7-ARDimW0</recordid><startdate>19980701</startdate><enddate>19980701</enddate><creator>Guan, Holly H</creator><creator>Budzynski, Wladyslaw</creator><creator>Koganty, R. Rao</creator><creator>Krantz, Mark J</creator><creator>Reddish, Mark A</creator><creator>Rogers, James A</creator><creator>Longenecker, B. Michael</creator><creator>Samuel, John</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19980701</creationdate><title>Liposomal Formulations of Synthetic MUC1 Peptides: Effects of Encapsulation versus Surface Display of Peptides on Immune Responses</title><author>Guan, Holly H ; Budzynski, Wladyslaw ; Koganty, R. Rao ; Krantz, Mark J ; Reddish, Mark A ; Rogers, James A ; Longenecker, B. Michael ; Samuel, John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a414t-33697694ee6af19e565e751b7b2026843f900fcc71358deeeb105eb1f754e43b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>AIDS/HIV</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibody Formation - drug effects</topic><topic>Antibody Specificity</topic><topic>Chemistry, Pharmaceutical</topic><topic>Cytokines - metabolism</topic><topic>Drug Carriers</topic><topic>Epitopes - analysis</topic><topic>Female</topic><topic>Humans</topic><topic>Liposomes</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Sequence Data</topic><topic>Mucin-1 - administration & dosage</topic><topic>Mucin-1 - immunology</topic><topic>Mucin-1 - pharmacology</topic><topic>Peptide Fragments - administration & dosage</topic><topic>Peptide Fragments - immunology</topic><topic>Peptide Fragments - pharmacology</topic><topic>Surface Properties</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - immunology</topic><topic>Th1 Cells - drug effects</topic><topic>Th1 Cells - immunology</topic><topic>Th1 Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guan, Holly H</creatorcontrib><creatorcontrib>Budzynski, Wladyslaw</creatorcontrib><creatorcontrib>Koganty, R. Rao</creatorcontrib><creatorcontrib>Krantz, Mark J</creatorcontrib><creatorcontrib>Reddish, Mark A</creatorcontrib><creatorcontrib>Rogers, James A</creatorcontrib><creatorcontrib>Longenecker, B. Michael</creatorcontrib><creatorcontrib>Samuel, John</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioconjugate chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guan, Holly H</au><au>Budzynski, Wladyslaw</au><au>Koganty, R. Rao</au><au>Krantz, Mark J</au><au>Reddish, Mark A</au><au>Rogers, James A</au><au>Longenecker, B. Michael</au><au>Samuel, John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liposomal Formulations of Synthetic MUC1 Peptides: Effects of Encapsulation versus Surface Display of Peptides on Immune Responses</atitle><jtitle>Bioconjugate chemistry</jtitle><addtitle>Bioconjugate Chem</addtitle><date>1998-07-01</date><risdate>1998</risdate><volume>9</volume><issue>4</issue><spage>451</spage><epage>458</epage><pages>451-458</pages><issn>1043-1802</issn><eissn>1520-4812</eissn><notes>istex:301F5AB58BE861D5D361EF6D36CED3766FEB5AB9</notes><notes>ark:/67375/TPS-TRWK6W4S-W</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Synthetic human MUC1 peptides are important candidates for therapeutic cancer vaccines. To explore whether a human MUC1 peptide BP25 (STAPPAHGVTSAPDTRPAPGSTAPP) can be rendered immunogenic by incorporation in liposomes, the effects of physical association of the peptide with liposomes on immune responses were investigated. Lipid conjugated and nonconjugated MUC1 peptides were incorporated in liposomes with a composition of distearoylphosphatidylcholine/cholesterol/dimyristoylphosphatidylglycerol (3:1:0.25, molar ratio) containing monophosphoryl lipid A (1% w/w of the total lipids). Liposomes were characterized for peptide retention by HPLC and for surface peptide display of MUC1 epitopes by flow cytometry. C57BL/6 mice were immunized with lipopeptide alone, peptide mixed with peptide-free liposomes, and peptide associated with liposomes in entrapped or surface-exposed forms. T cell proliferative responses, cytokine patterns, and antibody isotypes were studied. Results showed that immune responses were profoundly influenced by the liposome formulations. Physically associated, either encapsulated or surface-exposed, peptide liposomes elicited strong antigen-specific T cell responses, but not lipopeptide alone or peptide mixed with peptide-free liposomes. Analysis of the cytokines secreted by the proliferating T cells showed a high level of IFN-γ and undetectable levels of IL-4, indicating a T helper type 1 response. Thus, physical association of the peptide with liposomes was required for T cell proliferative responses, but the mode of association was not critical. On the other hand, the nature of the association significantly affected humoral immune responses. Only the surface-exposed peptide liposomes induced MUC1-specific antibodies. A domination of anti-MUC1 IgG2b over IgG1 (94 versus 6%) was observed. Our results support the hypothesis that different immune pathways are stimulated by different liposome formulations. This study demonstrated that a liposome delivery system could be tailored to induce either a preferential cellular or humoral immune response.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>9667946</pmid><doi>10.1021/bc970183n</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1043-1802 |
| ispartof | Bioconjugate chemistry, 1998-07, Vol.9 (4), p.451-458 |
| issn | 1043-1802 1520-4812 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_80008941 |
| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | AIDS/HIV Amino Acid Sequence Animals Antibodies, Monoclonal - immunology Antibody Formation - drug effects Antibody Specificity Chemistry, Pharmaceutical Cytokines - metabolism Drug Carriers Epitopes - analysis Female Humans Liposomes Lymphocyte Activation - drug effects Mice Mice, Inbred C57BL Molecular Sequence Data Mucin-1 - administration & dosage Mucin-1 - immunology Mucin-1 - pharmacology Peptide Fragments - administration & dosage Peptide Fragments - immunology Peptide Fragments - pharmacology Surface Properties T-Lymphocytes - drug effects T-Lymphocytes - immunology Th1 Cells - drug effects Th1 Cells - immunology Th1 Cells - metabolism |
| title | Liposomal Formulations of Synthetic MUC1 Peptides: Effects of Encapsulation versus Surface Display of Peptides on Immune Responses |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-21T10%3A50%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Liposomal%20Formulations%20of%20Synthetic%20MUC1%20Peptides:%E2%80%89%20Effects%20of%20Encapsulation%20versus%20Surface%20Display%20of%20Peptides%20on%20Immune%20Responses&rft.jtitle=Bioconjugate%20chemistry&rft.au=Guan,%20Holly%20H&rft.date=1998-07-01&rft.volume=9&rft.issue=4&rft.spage=451&rft.epage=458&rft.pages=451-458&rft.issn=1043-1802&rft.eissn=1520-4812&rft_id=info:doi/10.1021/bc970183n&rft_dat=%3Cproquest_cross%3E80008941%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-a414t-33697694ee6af19e565e751b7b2026843f900fcc71358deeeb105eb1f754e43b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=80008941&rft_id=info:pmid/9667946&rfr_iscdi=true |