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The CIt protocol: A blueprint to potentiate the immunogenicity of immunoproteasome-reprogrammed mesenchymal stromal cells.
Bikorimana, Jean-Pierre; El-Hachem, Nehme; Abusarah, Jamilah; Eliopoulos, Nicoletta; Talbot, Sebastien; Shammaa, Riam; Rafei, Moutih.
Afiliación
  • Bikorimana JP; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada.
  • El-Hachem N; Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada.
  • Abusarah J; Pediatric Hematology-Oncology Division, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC, Canada.
  • Eliopoulos N; Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada.
  • Talbot S; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.
  • Shammaa R; Department of Surgery, McGill University, Montreal, QC, Canada.
  • Rafei M; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
iScience ; 25(12): 105537, 2022 Dec 22.
Article en En | MEDLINE | ID: mdl-36437872
Immunoproteasome-reprogrammed mesenchymal stromal cells (IRMs) can surpass dendritic cells at eliciting tumor-specific immunity. However, the current IRM vaccination regimen remains clinically unsuitable due to the relatively high dose of IRMs needed. Since the administration of a lower IRM dose triggers a feeble anti-tumoral response, we aimed to combine this vaccination regimen with different modalities to fine-tune the potency of the vaccine. In a nutshell, we found that the co-administration of IRMs and interleukin-12 accentuates the anti-tumoral response, whereas the cross-presentation potency of IRMs is enhanced via intracellular succinate build-up, delayed endosomal maturation, and increased endosome-to-cytosol plasticity. Stimulating phagocyte-mediated cancer efferocytosis by blocking the CD47-SIRPα axis was also found to enhance IRM vaccine outcomes. Upon designing a single protocol combining the abovementioned strategies, 60% of treated animals exhibited a complete response. Altogether, this is the first IRM-based vaccination study, optimized to simultaneously target three vaccine-related pitfalls: T-cell response, antigen cross-presentation, and cancer phagocytosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline Idioma: En Revista: IScience Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline Idioma: En Revista: IScience Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos