Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects
Identifieur interne : 002392 ( Main/Exploration ); précédent : 002391; suivant : 002393Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects
Auteurs : Takuya Osada [États-Unis] ; Peter Berglund [États-Unis] ; Michael A. Morse [États-Unis] ; Bolyn Hubby [États-Unis] ; Whitney Lewis [États-Unis] ; Donna Niedzwiecki [États-Unis] ; Xiao Yi Yang [États-Unis] ; Amy Hobeika [États-Unis] ; Bruce Burnett [États-Unis] ; Gayathri R. Devi [États-Unis] ; Timothy M. Clay [États-Unis] ; Jonathan Smith [États-Unis] ; H. Kim Lyerly [États-Unis]Source :
- Cancer Immunology, Immunotherapy [ 0340-7004 ] ; 2012-11-01.
English descriptors
- KwdEn :
Abstract
Abstract: We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and antitumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)), and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12, and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP-IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing antitumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than that of VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted.
Url:
DOI: 10.1007/s00262-012-1248-y
Affiliations:
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Devi</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Duke University Medical Center, Box 2606 MSRB1 Rm 433b Research Dr, 27710, Durham, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Comprehensive Cancer Center, 27710, Durham, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Clay, Timothy M" sort="Clay, Timothy M" uniqKey="Clay T" first="Timothy M." last="Clay">Timothy M. Clay</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Duke University Medical Center, Box 2606 MSRB1 Rm 433b Research Dr, 27710, Durham, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunology, Duke University Medical Center, Durham, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Comprehensive Cancer Center, 27710, Durham, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Jonathan" sort="Smith, Jonathan" uniqKey="Smith J" first="Jonathan" last="Smith">Jonathan Smith</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Liquidia Technologies, RTP, 27709, Durham, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Kim Lyerly, H" sort="Kim Lyerly, H" uniqKey="Kim Lyerly H" first="H." last="Kim Lyerly">H. Kim Lyerly</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, Duke University Medical Center, Box 2606 MSRB1 Rm 433b Research Dr, 27710, Durham, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunology, Duke University Medical Center, Durham, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Duke Comprehensive Cancer Center, 27710, Durham, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Cancer Immunology, Immunotherapy</title><title level="j" type="abbrev">Cancer Immunol Immunother</title><idno type="ISSN">0340-7004</idno><idno type="eISSN">1432-0851</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2012-11-01">2012-11-01</date><biblScope unit="volume">61</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1941">1941</biblScope><biblScope unit="page" to="1951">1951</biblScope></imprint><idno type="ISSN">0340-7004</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0340-7004</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alphavirus</term><term>CEA</term><term>Cancer vaccine</term><term>Interleukin-12</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and antitumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)), and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12, and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP-IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing antitumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than that of VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Osada, Takuya" sort="Osada, Takuya" uniqKey="Osada T" first="Takuya" last="Osada">Takuya Osada</name></noRegion><name sortKey="Berglund, Peter" sort="Berglund, Peter" uniqKey="Berglund P" first="Peter" last="Berglund">Peter Berglund</name><name sortKey="Burnett, Bruce" sort="Burnett, Bruce" uniqKey="Burnett B" first="Bruce" last="Burnett">Bruce Burnett</name><name sortKey="Clay, Timothy M" sort="Clay, Timothy M" uniqKey="Clay T" first="Timothy M." last="Clay">Timothy M. Clay</name><name sortKey="Clay, Timothy M" sort="Clay, Timothy M" uniqKey="Clay T" first="Timothy M." last="Clay">Timothy M. Clay</name><name sortKey="Clay, Timothy M" sort="Clay, Timothy M" uniqKey="Clay T" first="Timothy M." last="Clay">Timothy M. Clay</name><name sortKey="Devi, Gayathri R" sort="Devi, Gayathri R" uniqKey="Devi G" first="Gayathri R." last="Devi">Gayathri R. Devi</name><name sortKey="Devi, Gayathri R" sort="Devi, Gayathri R" uniqKey="Devi G" first="Gayathri R." last="Devi">Gayathri R. Devi</name><name sortKey="Hobeika, Amy" sort="Hobeika, Amy" uniqKey="Hobeika A" first="Amy" last="Hobeika">Amy Hobeika</name><name sortKey="Hubby, Bolyn" sort="Hubby, Bolyn" uniqKey="Hubby B" first="Bolyn" last="Hubby">Bolyn Hubby</name><name sortKey="Kim Lyerly, H" sort="Kim Lyerly, H" uniqKey="Kim Lyerly H" first="H." last="Kim Lyerly">H. Kim Lyerly</name><name sortKey="Kim Lyerly, H" sort="Kim Lyerly, H" uniqKey="Kim Lyerly H" first="H." last="Kim Lyerly">H. Kim Lyerly</name><name sortKey="Kim Lyerly, H" sort="Kim Lyerly, H" uniqKey="Kim Lyerly H" first="H." last="Kim Lyerly">H. Kim Lyerly</name><name sortKey="Kim Lyerly, H" sort="Kim Lyerly, H" uniqKey="Kim Lyerly H" first="H." last="Kim Lyerly">H. Kim Lyerly</name><name sortKey="Lewis, Whitney" sort="Lewis, Whitney" uniqKey="Lewis W" first="Whitney" last="Lewis">Whitney Lewis</name><name sortKey="Morse, Michael A" sort="Morse, Michael A" uniqKey="Morse M" first="Michael A." last="Morse">Michael A. Morse</name><name sortKey="Morse, Michael A" sort="Morse, Michael A" uniqKey="Morse M" first="Michael A." last="Morse">Michael A. Morse</name><name sortKey="Niedzwiecki, Donna" sort="Niedzwiecki, Donna" uniqKey="Niedzwiecki D" first="Donna" last="Niedzwiecki">Donna Niedzwiecki</name><name sortKey="Smith, Jonathan" sort="Smith, Jonathan" uniqKey="Smith J" first="Jonathan" last="Smith">Jonathan Smith</name><name sortKey="Yang, Xiao Yi" sort="Yang, Xiao Yi" uniqKey="Yang X" first="Xiao Yi" last="Yang">Xiao Yi Yang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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