A1-reprogrammed mesenchymal stromal cells prime potent antitumoral responses
Marina Pereira Gonçalves,
Roudy Farah,
Jean-Pierre Bikorimana,
Jamilah Abusarah,
Nehme EL-Hachem,
Wael Saad,
Sebastien Talbot,
Daniela Stanga,
Simon Beaudoin,
Sebastien Plouffe,
Moutih Rafei
Affiliations
Marina Pereira Gonçalves
Molecular Biology Program, Université de Montréal, Montreal, QC, Canada
Roudy Farah
Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada
Jean-Pierre Bikorimana
Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada
Jamilah Abusarah
Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada
Nehme EL-Hachem
Pediatric Hematology-Oncology Division, Centre Hospitalier Universitaire Sainte-Justine Research Centre, Montreal, QC, Canada
Wael Saad
Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada
Sebastien Talbot
Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada
Daniela Stanga
Defence Therapeutics Inc., Research and Development branch, Montreal, QC, Canada
Simon Beaudoin
Defence Therapeutics Inc., Research and Development branch, Montreal, QC, Canada
Sebastien Plouffe
Defence Therapeutics Inc., Research and Development branch, Montreal, QC, Canada
Moutih Rafei
Molecular Biology Program, Université de Montréal, Montreal, QC, Canada; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada; Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada; Corresponding author
Summary: 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 of a variant library of Accum molecule revealed a molecule (A1) capable of eliciting antigen cross-presentation properties in MSCs. A1-reprogrammed MSCs (ARM) exhibited improved soluble antigen uptake and processing. Our comprehensive analysis, encompassing cross-presentation assays and molecular profiling, among other cellular investigations, elucidated A1’s impact on endosomal escape, reactive oxygen species production, and cytokine secretion. By evaluating ARM-based cellular vaccine in mouse models of lymphoma and melanoma, we observe significant therapeutic potency, particularly in allogeneic setting and in combination with anti-PD-1 immune checkpoint inhibitor. Overall, this study introduces a strong target for developing an antigen-adaptable vaccination platform, capable of synergizing with immune checkpoint blockers to trigger tumor regression, supporting further investigation of ARMs as an effective and versatile anti-cancer vaccine.
