Evaluation of Galsome vaccination in multiple myeloma

Edith Maria Janssens, Lien De Beck, Rein Verbeke, Ine Lentacker, Heleen Dewitte, Eline Menu, Karine Breckpot

Research output: Unpublished contribution to conferenceUnpublished abstract

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.
Original languageEnglish
Pages1
Number of pages1
Publication statusUnpublished - 23 Jun 2021
EventMOSA conference - Maastricht, Maastricht, Netherlands
Duration: 23 Jun 202123 Jun 2021
http://www.mosa-conference.com/

Conference

ConferenceMOSA conference
CountryNetherlands
CityMaastricht
Period23/06/2123/06/21
Internet address

Keywords

  • mRNA
  • vaccine
  • cancer
  • immunotherapy

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