Targeted DNA vaccines for enhanced induction of Idiotype (Id)-specific B and T cells
Background: Idiotopes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id+ tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id+ single chain Fragment variable (sc...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00154/full |
| _version_ | 1818608319308234752 |
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| author | Agnete Brunsvik Fredriksen Inger eSandlie Bjarne eBogen |
| author_facet | Agnete Brunsvik Fredriksen Inger eSandlie Bjarne eBogen |
| author_sort | Agnete Brunsvik Fredriksen |
| collection | DOAJ |
| description | Background: Idiotopes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id+ tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id+ single chain Fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHCII, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id+ fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id+ tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id+ scFv from 4 multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusions: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients. |
| first_indexed | 2024-12-16T14:40:45Z |
| format | Article |
| id | doaj.art-b253c16077df4069a5ee971c106bb3fb |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-16T14:40:45Z |
| publishDate | 2012-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b253c16077df4069a5ee971c106bb3fb2022-12-21T22:27:56ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2012-10-01210.3389/fonc.2012.0015436351Targeted DNA vaccines for enhanced induction of Idiotype (Id)-specific B and T cellsAgnete Brunsvik Fredriksen0Inger eSandlie1Bjarne eBogen2University of Oslo and Oslo University HospitalUniversity of Oslo and Oslo University HospitalUniversity of Oslo and Oslo University HospitalBackground: Idiotopes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id+ tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id+ single chain Fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHCII, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id+ fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id+ tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id+ scFv from 4 multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusions: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00154/fullLymphomaMultiple MyelomaVaccineantigen presenting cellsIdiotype |
| spellingShingle | Agnete Brunsvik Fredriksen Inger eSandlie Bjarne eBogen Targeted DNA vaccines for enhanced induction of Idiotype (Id)-specific B and T cells Frontiers in Oncology Lymphoma Multiple Myeloma Vaccine antigen presenting cells Idiotype |
| title | Targeted DNA vaccines for enhanced induction of Idiotype (Id)-specific B and T cells |
| title_full | Targeted DNA vaccines for enhanced induction of Idiotype (Id)-specific B and T cells |
| title_fullStr | Targeted DNA vaccines for enhanced induction of Idiotype (Id)-specific B and T cells |
| title_full_unstemmed | Targeted DNA vaccines for enhanced induction of Idiotype (Id)-specific B and T cells |
| title_short | Targeted DNA vaccines for enhanced induction of Idiotype (Id)-specific B and T cells |
| title_sort | targeted dna vaccines for enhanced induction of idiotype id specific b and t cells |
| topic | Lymphoma Multiple Myeloma Vaccine antigen presenting cells Idiotype |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00154/full |
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