Details

Autor(en) / Beteiligte

• Abusarah, Jamilah
• Khodayarian, Fatemeh
• El-Hachem, Nehme
• Salame, Natasha
• Olivier, Martin
• Balood, Mohammad
• Roversi, Katiane
• Talbot, Sebastien
• Bikorimana, Jean-Pierre
• Chen, Jingkui
• Jolicoeur, Mario
• Trudeau, Louis-Eric
• Kamyabiazar, Samaneh
• Annabi, Borhane
• Robert, Francis
• Pelletier, Jerry
• El-Kadiry, Abed-El-Hakim
• Shammaa, Riam
• Rafei, Moutih

Titel

Engineering immunoproteasome-expressing mesenchymal stromal cells: A potent cellular vaccine for lymphoma and melanoma in mice

Ist Teil von

• Cell reports. Medicine, 2021-12, Vol.2 (12), p.100455-100455, Article 100455

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Dendritic cells (DCs) excel at cross-presenting antigens, but their effectiveness as cancer vaccine is limited. Here, we describe a vaccination approach using mesenchymal stromal cells (MSCs) engineered to express the immunoproteasome complex (MSC-IPr). Such modification instills efficient antigen cross-presentation abilities associated with enhanced major histocompatibility complex class I and CD80 expression, de novo production of interleukin-12, and higher chemokine secretion. This cross-presentation capacity of MSC-IPr is highly dependent on their metabolic activity. Compared with 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 and A20 lymphomas and B16 melanoma tumors. Moreover, therapeutic vaccination of mice with pre-established tumors efficiently controls cancer growth, an effect further enhanced when combined with antibodies targeting PD-1, CTLA4, LAG3, or 4-1BB under both autologous and allogeneic settings. Therefore, MSC-IPr constitute a promising subset of non-hematopoietic antigen-presenting cells suitable for designing universal cell-based cancer vaccines. [Display omitted] •Stable expression of the immunoproteasome in MSCs instills a pro-inflammatory phenotype•Induced metabolic alterations drive antigen cross-presentation by MSC-IPr•Engineered MSC-IPr elicit potent anti-tumoral immunity•The immunopeptidome of MSC-IPr is distinct from dendritic cells Abusarah et al. demonstrate that mesenchymal stromal cells engineered to express the immunoproteasome (MSC-IPr) exhibit distinct antigen presentation properties, display altered metabolic signatures, and present a unique set of antigens compared with standard dendritic cells. These attributes make them ideal candidates for the future design of cell-based cancer vaccines.