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Engineering a Potent Cancer Vaccine Using Immunoproteasome-Expressing Mesenchymal Stromal Cells

78 Pages Posted: 9 Feb 2021 Publication Status: Review Complete

See all articles by Jamilah Abusarah

Jamilah Abusarah

McGill University - Department of Microbiology and Immunology

Fatemeh Khodayarian

University of Montreal - Department of Pharmacology and Physiology

Nehme El-Hachem

University of Montreal - Department of Pharmacology and Physiology

Natasha Salame

Université de Montréal - Department of Biomedical Sciences

Martin Olivier

McGill University - Department of Microbiology and Immunology

Mohammad Balood

University of Montreal - Department of Pharmacology and Physiology

Katiane Roversi

University of Montreal - Department of Pharmacology and Physiology

Sebastien Talbot

University of Montreal - Department of Pharmacology and Physiology

Jean-Pierre Bikorimana

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

Jingkui Chen

Polytechnique Montréal - Research Laboratory in Applied Metabolic Engineering

Mario Jolicoeur

Polytechnique Montréal - Research Laboratory in Applied Metabolic Engineering

Louis-Eric Trudeau

University of Montreal - Department of Pharmacology and Physiology

Samaneh Kamyabiazar

Université du Québec à Montréal - Department of Chemistry

Borhane Annabi

Université du Québec à Montréal - Department of Chemistry

Francis Robert

McGill University - Department of Biochemistry

Jerry Pelletier

McGill University - Department of Biochemistry

Abed El-Kadiry

University of Montreal - Department of Pharmacology and Physiology

Riam Shammaa

University of Toronto - Department of Family and Community Medicine

Moutih Rafei

University of Montreal - Department of Pharmacology and Physiology

More...

Abstract

Dendritic cells (DCs) excel at cross-presenting antigens, but their effectiveness as cancer vaccine is limited. Here, we describe an innovative vaccine approach using mesenchymal stromal cells (MSCs) engineered to express the immunoproteasome (IPr) complex (MSC-IPr). Such modification instilled efficient antigen cross-presenting abilities associated with enhanced major histocompatibility complex (MHC)I and CD80 expression, de novo expression of interleukin-12 along with higher chemokine secretion. In addition, the cross-presentation capacity of MSC-IPr is highly dependent on AMPK signaling, oxidative phosphorylation and production of reactive oxygen species. Compared to DCs, MSC-IPr hold the ability to cross-present a vastly different epitope repertoire, which translates into potent re-activation of T-cell immunity against EL4 lymphoma and B16 melanoma tumors. Moreover, therapeutic vaccination of animals with pre-established tumors efficiently controls cancer growth, an effect further enhanced when combined with antibodies targeting PD1, CTLA4, LAG3 or 4-1BB under both autologous and allogeneic settings. MSC-IPr constitute therefore a novel subset of non-hematopoietic antigen-presenting cells suitable for the future design of universal cell-based cancer vaccines.

Keywords: Immunoproteasome, Mesenchymal Stromal Cells, Cancer Vaccine, SILACs, Transcriptomics, Metabolomics, Immunopeptidome, Immune-Checkpoint blockers, Universal Vaccine

Suggested Citation

Abusarah, Jamilah and Khodayarian, Fatemeh and El-Hachem, Nehme and Salame, Natasha and Olivier, Martin and Balood, Mohammad and Roversi, Katiane and Talbot, Sebastien and Bikorimana, Jean-Pierre and Chen, Jingkui and Jolicoeur, Mario and Trudeau, Louis-Eric and Kamyabiazar, Samaneh and Annabi, Borhane and Robert, Francis and Pelletier, Jerry and El-Kadiry, Abed and Shammaa, Riam and Rafei, Moutih, Engineering a Potent Cancer Vaccine Using Immunoproteasome-Expressing Mesenchymal Stromal Cells. Available at SSRN: https://ssrn.com/abstract=3782860 or http://dx.doi.org/10.2139/ssrn.3782860
This version of the paper has not been formally peer reviewed.

Jamilah Abusarah

McGill University - Department of Microbiology and Immunology

Canada

Fatemeh Khodayarian

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

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

Nehme El-Hachem

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

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

Natasha Salame

Université de Montréal - Department of Biomedical Sciences ( email )

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

Martin Olivier

McGill University - Department of Microbiology and Immunology ( email )

Canada

Mohammad Balood

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

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

Katiane Roversi

University of Montreal - Department of Pharmacology and Physiology

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

Sebastien Talbot

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

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

Jean-Pierre Bikorimana

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

University of Montreal
Montreal, QC

Jingkui Chen

Polytechnique Montréal - Research Laboratory in Applied Metabolic Engineering ( email )

Canada

Mario Jolicoeur

Polytechnique Montréal - Research Laboratory in Applied Metabolic Engineering ( email )

Canada

Louis-Eric Trudeau

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

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

Samaneh Kamyabiazar

Université du Québec à Montréal - Department of Chemistry ( email )

PB 8888 Station DownTown
Succursale Centre Ville
Montreal, Quebec H3C3P8
Canada

Borhane Annabi

Université du Québec à Montréal - Department of Chemistry ( email )

PB 8888 Station DownTown
Succursale Centre Ville
Montreal, Quebec H3C3P8
Canada

Francis Robert

McGill University - Department of Biochemistry ( email )

1001 Sherbrooke St. W
Montreal, Quebec H3A 1G5
Canada

Jerry Pelletier

McGill University - Department of Biochemistry ( email )

1001 Sherbrooke St. W
Montreal, Quebec H3A 1G5
Canada

Abed El-Kadiry

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

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

Riam Shammaa

University of Toronto - Department of Family and Community Medicine ( email )

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

Moutih Rafei (Contact Author)

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

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

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