puc-header

The CIt Protocol: A Blueprint to Potentiate the Immunogenicity of Immunoproteasome-Reprogrammed Mesenchymal Stromal Cells

51 Pages Posted: 18 Jul 2022 Publication Status: Accepted

See all articles by Jean Pierre Bikorimana

Jean Pierre Bikorimana

University of Montreal - Department of Microbiology, Infectious Diseases and Immunology

Nehme El-Hachem

University of Montreal - Department of Pharmacology and Physiology

Jamilah Abusarah

University of Montreal - Department of Pharmacology and Physiology

Nicoletta Eliopoulos

McGill University - Department of Surgery

Sebastien Talbot

University of Montreal - Department of Pharmacology and Physiology

Riam Shammaa

IntelliStem Technologies Inc.

Moutih Rafei

University of Montreal - Department of Pharmacology and Physiology

More...

Abstract

SUMMARYImmunoproteasome-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 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 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 phagocytemediated 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.

Funding Information: This work was supported by an operating grant from the Cancer Research Society (#OG834469), an innovation to impact grant from the Canadian Cancer Society (#706201), and a Discovery grant from the National Research and Engineering Council of Canada (#RGPIN/06101-2014).

Declaration of Interests: The authors declare no competing financial interests.

Ethics Approval Statement: All animal protocols were approved by the Animal Care Committee (CDEA) of Université de Montréal.

Suggested Citation

Bikorimana, Jean Pierre and El-Hachem, Nehme and Abusarah, Jamilah and Eliopoulos, Nicoletta and Talbot, Sebastien and Shammaa, Riam and Rafei, Moutih, The CIt Protocol: A Blueprint to Potentiate the Immunogenicity of Immunoproteasome-Reprogrammed Mesenchymal Stromal Cells. Available at SSRN: https://ssrn.com/abstract=4166327 or http://dx.doi.org/10.2139/ssrn.4166327
This version of the paper has not been formally peer reviewed.

Jean Pierre Bikorimana

University of Montreal - Department of Microbiology, Infectious Diseases and Immunology ( email )

University of Montreal
Montreal, QC

Nehme El-Hachem

University of Montreal - Department of Pharmacology and Physiology ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Jamilah Abusarah

University of Montreal - Department of Pharmacology and Physiology ( email )

Nicoletta Eliopoulos

McGill University - Department of Surgery ( email )

Sebastien Talbot

University of Montreal - Department of Pharmacology and Physiology ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Riam Shammaa

IntelliStem Technologies Inc. ( email )

Moutih Rafei (Contact Author)

University of Montreal - Department of Pharmacology and Physiology ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Click here to go to Cell.com

Paper statistics

Abstract Views
79
Downloads
2
PlumX Metrics