A1-reprogrammed mesenchymal stromal cells prime potent antitumoral responses

• DOI: 10.1016/j.isci.2024.109248
• Publication Date: 2024-02-17T02:50:22Z
• Authors: Marina Pereira Go...; Roudy Farah; Jean-Pierre Bikor...; Jamilah Abusarah; Nehme EL-Hachem; Wael Saad; Sebastien Talbot; Daniela Stanga; Simon Beaudoin; Sebastien Plouffe; Moutih Rafei
• Keywords: Cross-Presentation; Immune checkpoint; Cancer Immunotherapy

Mesenchymal stromal cells (MSCs) have been modified via genetic or pharmacological engineering into potent antigen-presenting cells-like capable of priming responding CD8 T cells. In this study, our screening a variant library Accum molecule revealed (A1) eliciting antigen cross-presentation properties in MSCs. A1-reprogrammed MSCs (ARM) exhibited improved soluble uptake and processing. Our comprehensive analysis, encompassing assays molecular profiling, among other cellular investigations, elucidated A1's impact on endosomal escape, reactive oxygen species production, cytokine secretion. By evaluating ARM-based vaccine mouse models lymphoma melanoma, we observe significant therapeutic potency, particularly allogeneic setting combination with anti-PD-1 immune checkpoint inhibitor. Overall, study introduces strong target for developing an antigen-adaptable vaccination platform, synergizing blockers to trigger tumor regression, supporting further investigation ARMs as effective versatile anti-cancer vaccine.