Projects per year
Abstract
Introduction: Multiple myeloma (MM), a plasma cell malignancy, is an incurable hema-tological cancer for which immunotherapy is actively pursued as a treatment option. We studied Galsomes, a lipid nanoparticle vaccine, for treatment of MM. Galsomes contain tumor antigen mRNA and glycolipids to activate CD8+ T-cells (TCs) and invariant natural killer T-cells (iNKTs), as such tackling MM-cells from different angles.
Materials and methods: Galsomes, loaded with gp100 and survivin mRNA and alpha-galactosylceramide, were prepared for intravenous delivery to C57bl/kalwrij mice bearing 5T33MM-cells. Mice were injected twice with Galsomes or saline (control). Development of MM was monitored. Immune activation and changes in the spleen and bone marrow, the MM-microenvironment, were evaluated upon a single Galsome injection. ELISA was used to measure interferon-gamma by TCs and iNKTs, while flow cytometry was used to study the MM-microenvironment. Statistical analysis was performed using GraphPad Prism 9.
Results: Delayed MM-development was not observed upon prime-boost vaccination with Galsomes. Serum interferon-gamma levels were increased 5 hours after a single Galsome injection, signifying NKT-activation. However, interferon-gamma production by TCs isolated from spleen upon restimulation with gp100 or survivin was not increased as a result of Galsome vaccination, despite higher TC-numbers in the spleen. Stimulation of these TCs with a broad TC-activating stimulus showed that they were dysfunctional. Little differences were observed in other immune cell populations, with the exception of conventional type 2 dendritic cells (cDC2s) which were increased upon Galsome vaccination.
Conclusion: Preliminary data suggest that Galsome vaccination in the 5T33MM-model is not successful despite activation of NKTs and increased TC-percentages. This is likely explained by the TCs’ inability to produce interferon-gamma. Future experiments will be designed to address this TC-dysfunctionality. As the role of cDC2s in MM is not yet described, future experiments will address whether these cells can help fight MM or not.
Materials and methods: Galsomes, loaded with gp100 and survivin mRNA and alpha-galactosylceramide, were prepared for intravenous delivery to C57bl/kalwrij mice bearing 5T33MM-cells. Mice were injected twice with Galsomes or saline (control). Development of MM was monitored. Immune activation and changes in the spleen and bone marrow, the MM-microenvironment, were evaluated upon a single Galsome injection. ELISA was used to measure interferon-gamma by TCs and iNKTs, while flow cytometry was used to study the MM-microenvironment. Statistical analysis was performed using GraphPad Prism 9.
Results: Delayed MM-development was not observed upon prime-boost vaccination with Galsomes. Serum interferon-gamma levels were increased 5 hours after a single Galsome injection, signifying NKT-activation. However, interferon-gamma production by TCs isolated from spleen upon restimulation with gp100 or survivin was not increased as a result of Galsome vaccination, despite higher TC-numbers in the spleen. Stimulation of these TCs with a broad TC-activating stimulus showed that they were dysfunctional. Little differences were observed in other immune cell populations, with the exception of conventional type 2 dendritic cells (cDC2s) which were increased upon Galsome vaccination.
Conclusion: Preliminary data suggest that Galsome vaccination in the 5T33MM-model is not successful despite activation of NKTs and increased TC-percentages. This is likely explained by the TCs’ inability to produce interferon-gamma. Future experiments will be designed to address this TC-dysfunctionality. As the role of cDC2s in MM is not yet described, future experiments will address whether these cells can help fight MM or not.
Original language | English |
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Pages | 1 |
Number of pages | 1 |
Publication status | Unpublished - 23 Jun 2021 |
Event | MOSA conference - Maastricht, Maastricht, Netherlands Duration: 23 Jun 2021 → 23 Jun 2021 http://www.mosa-conference.com/ |
Conference
Conference | MOSA conference |
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Country/Territory | Netherlands |
City | Maastricht |
Period | 23/06/21 → 23/06/21 |
Internet address |
Keywords
- mRNA
- vaccine
- cancer
- immunotherapy
Fingerprint
Dive into the research topics of 'Evaluation of Galsome vaccination in multiple myeloma'. Together they form a unique fingerprint.Projects
- 3 Finished
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FWOAL934: Smart design nanoParticles to Activate immune Responses against Cancer (SPARC)
Breckpot, K., Keyaerts, M., Barbé, K. & De Smedt, S.
1/01/19 → 31/12/22
Project: Fundamental
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FWOTM900: Modulating epigenetic mechanisms to enhance cancer immunotherapy.
Breckpot, K., De Beck, L. & Maes, K.
1/10/18 → 30/09/22
Project: Fundamental
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SRP48: Strategic Research Programme: Cancer Cell Targeting in Myeloma and Melanoma (MyMe)
Vanderkerken, K., Thielemans, K., Vanderkerken, K. & Breckpot, K.
1/11/17 → 31/10/24
Project: Fundamental
Prizes
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Best Oral Presentation - MOSA conference 2021
Janssens, Edith Maria (Recipient), De Beck, Lien (Recipient), Verbeke, Rein (Recipient), Lentacker, Ine (Recipient), Dewitte, Heleen (Recipient), Menu, Eline (Recipient) & Breckpot, Karine (Recipient), 23 Jun 2021
Prize: Prize (including medals and awards)
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