Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist
The tumor vaccine MGN1601 was designed and developed for treatment of metastatic renal cell carcinoma (mRCC). MGN1601 consists of a combination of fourfold gene-modified cells with the toll-like receptor 9 agonist dSLIM, a powerful connector of innate and adaptive immunity. Vaccine cells originate f...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | Molecular Therapy: Oncolytics |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770516300316 |
| _version_ | 1818541399525556224 |
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| author | Barbara Volz Manuel Schmidt Kerstin Heinrich Kerstin Kapp Matthias Schroff Burghardt Wittig |
| author_facet | Barbara Volz Manuel Schmidt Kerstin Heinrich Kerstin Kapp Matthias Schroff Burghardt Wittig |
| author_sort | Barbara Volz |
| collection | DOAJ |
| description | The tumor vaccine MGN1601 was designed and developed for treatment of metastatic renal cell carcinoma (mRCC). MGN1601 consists of a combination of fourfold gene-modified cells with the toll-like receptor 9 agonist dSLIM, a powerful connector of innate and adaptive immunity. Vaccine cells originate from a renal cell carcinoma cell line (grown from renal cell carcinoma tissue), express a variety of known tumor-associated antigens (TAA), and are gene modified to transiently express two co-stimulatory molecules, CD80 and CD154, and two cytokines, GM-CSF and IL-7, aimed to support immune response. Proof of concept of the designed vaccine was shown in mice: The murine homologue of the vaccine efficiently (100%) prevented tumor growth when used as prophylactic vaccine in a syngeneic setting. Use of the vaccine in a therapeutic setting showed complete response in 92% of mice as well as synergistic action and necessity of the components. In addition, specific cellular and humoral immune responses in mice were found when used in an allogeneic setting. Immune response to the vaccine was also shown in mRCC patients treated with MGN1601: Peptide array analysis revealed humoral CD4-based immune response to TAA expressed on vaccine cells, including survivin, cyclin D1, and stromelysin. |
| first_indexed | 2024-12-11T22:08:47Z |
| format | Article |
| id | doaj.art-d6d316b31c4c4525a5697f6c8061be34 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-11T22:08:47Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-d6d316b31c4c4525a5697f6c8061be342022-12-22T00:48:52ZengElsevierMolecular Therapy: Oncolytics2372-77052016-01-013C10.1038/mto.2015.23Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonistBarbara Volz0Manuel Schmidt1Kerstin Heinrich2Kerstin Kapp3Matthias Schroff4Burghardt Wittig5Foundation Institute for Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Berlin, GermanyMologen AG, Berlin, GermanyFoundation Institute for Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Berlin, GermanyMologen AG, Berlin, GermanyMologen AG, Berlin, GermanyFoundation Institute for Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Berlin, GermanyThe tumor vaccine MGN1601 was designed and developed for treatment of metastatic renal cell carcinoma (mRCC). MGN1601 consists of a combination of fourfold gene-modified cells with the toll-like receptor 9 agonist dSLIM, a powerful connector of innate and adaptive immunity. Vaccine cells originate from a renal cell carcinoma cell line (grown from renal cell carcinoma tissue), express a variety of known tumor-associated antigens (TAA), and are gene modified to transiently express two co-stimulatory molecules, CD80 and CD154, and two cytokines, GM-CSF and IL-7, aimed to support immune response. Proof of concept of the designed vaccine was shown in mice: The murine homologue of the vaccine efficiently (100%) prevented tumor growth when used as prophylactic vaccine in a syngeneic setting. Use of the vaccine in a therapeutic setting showed complete response in 92% of mice as well as synergistic action and necessity of the components. In addition, specific cellular and humoral immune responses in mice were found when used in an allogeneic setting. Immune response to the vaccine was also shown in mRCC patients treated with MGN1601: Peptide array analysis revealed humoral CD4-based immune response to TAA expressed on vaccine cells, including survivin, cyclin D1, and stromelysin.http://www.sciencedirect.com/science/article/pii/S2372770516300316 |
| spellingShingle | Barbara Volz Manuel Schmidt Kerstin Heinrich Kerstin Kapp Matthias Schroff Burghardt Wittig Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist Molecular Therapy: Oncolytics |
| title | Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist |
| title_full | Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist |
| title_fullStr | Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist |
| title_full_unstemmed | Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist |
| title_short | Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist |
| title_sort | design and characterization of the tumor vaccine mgn1601 allogeneic fourfold gene modified vaccine cells combined with a tlr 9 agonist |
| url | http://www.sciencedirect.com/science/article/pii/S2372770516300316 |
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