1. Engineering a Potent Cancer Vaccine Using Immunoproteasome-Expressing Mesenchymal Stromal Cells
- Author
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Jingkui Chen, Jamilah Abusarah, Jean-Pierre Bikorimana, Francis Robert, Borhane Annabi, Natasha Salame, Riam Shammaa, Sébastien Talbot, Mario Jolicoeur, Moutih Rafei, Fatemeh Khodayarian, Mohammad Balood, Abed El-Hakim El-Kadiry, Nehme El-Hachem, Samaneh Kamyabiazar, Martin Olivier, Katiane Roversi, Louis-Eric Trudeau, and Jerry Pelletier
- Subjects
LAG3 ,biology ,Mesenchymal stem cell ,Cancer ,chemical and pharmacologic phenomena ,medicine.disease ,Major histocompatibility complex ,Epitope ,Antigen ,Chemokine secretion ,medicine ,biology.protein ,Cancer research ,Cancer vaccine - 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.
- Published
- 2021