Evaluation of Galsome vaccination in multiple myeloma

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.