PXD060156

PXD060156 is an original dataset announced via ProteomeXchange.

Title	Exploring omics-identified antigens and mRNA-lipid nanoparticle vaccines with alpha-galactosylceramide for multiple myeloma therapy
Description	Introduction: Natural killer T (NKT) cells and CD8+ T cells are key in the immune response against multiple myeloma (MM), a largely incurable blood cancer. Immunization is a promising strategy to activate these T cell populations. To our knowledge, immunization with mRNA and α-galactosyl ceramide (αGC) have not been studied in MM, as knowledge on clinically relevant antigens in preclinical MM models is lacking. Methods: Transcriptomics and immunopeptidomics were used to identify candidate antigens for immunization in 5TMM models. Galsomes, lipid nanoparticles containing antigen mRNA and αGC were used to immunize 5T33MM bearing mice. This treatment was combined with a CD40 agonist. Tumor burden and activation of NKT cells and CD8+ T cells were studied using M-protein electrophoresis, cytospin, flow cytometry and ELISA. Results: Transcriptomics revealed survivin as a candidate antigen. Prime-boost Galsomes therapy targeting survivin significantly reduced M-protein levels despite low survivin-specific T cell responses. Further analysis showed potential T cell fratricide. Immunopeptidomics revealed HSP60, Idiotype, PICALM and EF1A1 as candidate antigens. Prime-boost therapy with Galsomes targeting these antigens reduced MM growth significantly when combined with a CD40 agonist, coinciding with significantly improved antigen presentation, co-stimulation and cytotoxicity of NKT cells and CD8+ T cells. Conclusion: These findings highlight the potential of Galsomes, an mRNA vaccine designed to activate CD8+ T cells and NKT cells, for MM therapy, and emphasize the importance of combinatorial approaches, addressing immune anergy for effective MM immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_06:58:47.267.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabien Thery
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-24 06:27:59	ID requested
⏵ 1	2025-05-07 06:58:48	announced

Van der Vreken A, Thery F, Tu C, Mwangi K, Meulewaeter S, De Beck L, Janssens E, De Veirman K, Vanderkerken K, De Bruyne E, Franceschini L, Impens F, Verbeke R, Lentacker I, Menu E, Breckpot K, Immunopeptidomics identified antigens for mRNA-lipid nanoparticle vaccines with alpha-galactosylceramide in multiple myeloma therapy. J Immunother Cancer, 13(4):(2025) [pubmed]

10.1136/jitc-2024-010673;

submitter keyword: cancer, myeloma, mouse,immunopeptidomics

Prof. Francis Impens
contact affiliation	VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
contact email	francis.impens@vib-ugent.be
lab head
Fabien Thery
contact affiliation	VIB-UGent
contact email	fabien.thery91@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060156
     1. Label: PRIDE project
     2. Name: Exploring omics-identified antigens and mRNA-lipid nanoparticle vaccines with alpha-galactosylceramide for multiple myeloma therapy