PMID- 35028603
OWN - NLM
STAT- MEDLINE
DCOM- 20220303
LR  - 20240226
IS  - 2666-3791 (Electronic)
IS  - 2666-3791 (Linking)
VI  - 2
IP  - 12
DP  - 2021 Dec 21
TI  - Engineering immunoproteasome-expressing mesenchymal stromal cells: A potent 
      cellular vaccine for lymphoma and melanoma in mice.
PG  - 100455
LID - 10.1016/j.xcrm.2021.100455 [doi]
LID - 100455
AB  - 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.
CI  - (c) 2021 The Authors.
FAU - Abusarah, Jamilah
AU  - Abusarah J
AD  - Department of Microbiology and Immunology, McGill University, Montreal, QC, 
      Canada.
FAU - Khodayarian, Fatemeh
AU  - Khodayarian F
AD  - Department of Pharmacology and Physiology, Universite de Montreal, Montreal, QC, 
      Canada.
FAU - El-Hachem, Nehme
AU  - El-Hachem N
AD  - Department of Pharmacology and Physiology, Universite de Montreal, Montreal, QC, 
      Canada.
FAU - Salame, Natasha
AU  - Salame N
AD  - Department of Biomedical Sciences, Universite de Montreal, Montreal, QC, Canada.
FAU - Olivier, Martin
AU  - Olivier M
AD  - Department of Microbiology and Immunology, McGill University, Montreal, QC, 
      Canada.
FAU - Balood, Mohammad
AU  - Balood M
AD  - Department of Pharmacology and Physiology, Universite de Montreal, Montreal, QC, 
      Canada.
FAU - Roversi, Katiane
AU  - Roversi K
AD  - Department of Pharmacology and Physiology, Universite de Montreal, Montreal, QC, 
      Canada.
FAU - Talbot, Sebastien
AU  - Talbot S
AD  - Department of Pharmacology and Physiology, Universite de Montreal, Montreal, QC, 
      Canada.
FAU - Bikorimana, Jean-Pierre
AU  - Bikorimana JP
AD  - Department of Microbiology, Infectious Diseases and Immunology, Universite de 
      Montreal, Montreal, QC, Canada.
FAU - Chen, Jingkui
AU  - Chen J
AD  - Research Laboratory in Applied Metabolic Engineering, Department of Chemical 
      Engineering, Polytechnique Montreal, Montreal, QC, Canada.
FAU - Jolicoeur, Mario
AU  - Jolicoeur M
AD  - Research Laboratory in Applied Metabolic Engineering, Department of Chemical 
      Engineering, Polytechnique Montreal, Montreal, QC, Canada.
FAU - Trudeau, Louis-Eric
AU  - Trudeau LE
AD  - Department of Pharmacology and Physiology, Universite de Montreal, Montreal, QC, 
      Canada.
FAU - Kamyabiazar, Samaneh
AU  - Kamyabiazar S
AD  - Department of Chemistry, Universite du Quebec a Montreal, Montreal, QC, Canada.
FAU - Annabi, Borhane
AU  - Annabi B
AD  - Department of Chemistry, Universite du Quebec a Montreal, Montreal, QC, Canada.
FAU - Robert, Francis
AU  - Robert F
AD  - Department of Biochemistry, McGill University, Montreal, QC, Canada.
FAU - Pelletier, Jerry
AU  - Pelletier J
AD  - Department of Biochemistry, McGill University, Montreal, QC, Canada.
FAU - El-Kadiry, Abed-El-Hakim
AU  - El-Kadiry AE
AD  - Department of Pharmacology and Physiology, Universite de Montreal, Montreal, QC, 
      Canada.
FAU - Shammaa, Riam
AU  - Shammaa R
AD  - Department of Family and Community Medicine, University of Toronto, Toronto, ON, 
      Canada.
AD  - Canadian Centers for Regenerative Therapy, Toronto, ON, Canada.
AD  - IntelliStem Technologies Inc., Toronto, ON, Canada.
FAU - Rafei, Moutih
AU  - Rafei M
AD  - Department of Microbiology and Immunology, McGill University, Montreal, QC, 
      Canada.
AD  - Department of Pharmacology and Physiology, Universite de Montreal, Montreal, QC, 
      Canada.
AD  - Department of Microbiology, Infectious Diseases and Immunology, Universite de 
      Montreal, Montreal, QC, Canada.
AD  - Molecular Biology Program, Universite de Montreal, Montreal, QC, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211221
PL  - United States
TA  - Cell Rep Med
JT  - Cell reports. Medicine
JID - 101766894
RN  - 0 (Cancer Vaccines)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - Antigen-Presenting Cells/immunology
MH  - Cancer Vaccines/*immunology
MH  - Cellular Reprogramming
MH  - Dendritic Cells/immunology
MH  - Female
MH  - Immune Checkpoint Inhibitors/pharmacology
MH  - Immunity
MH  - Lymphoma/*immunology
MH  - Melanoma, Experimental/*immunology
MH  - Mesenchymal Stem Cells/*immunology
MH  - Mice, Inbred C57BL
MH  - Oxidative Phosphorylation
MH  - Phenotype
MH  - Proteasome Endopeptidase Complex/*immunology
MH  - *Protein Engineering
MH  - Vaccination
MH  - Mice
PMC - PMC8714858
OTO - NOTNLM
OT  - SILACs
OT  - cancer vaccine
OT  - immune-checkpoint blockers
OT  - immunopeptidome
OT  - immunoproteasome
OT  - mesenchymal stromal cells
OT  - metabolomics
OT  - transcriptomics
OT  - universal vaccine
COIS- The authors declare no competing financial interests. A provisional patent has 
      been filed to protect the MSC-IPr technology and its applications (62/835,678).
EDAT- 2022/01/15 06:00
MHDA- 2022/03/04 06:00
PMCR- 2021/12/21
CRDT- 2022/01/14 06:09
PHST- 2021/02/05 00:00 [received]
PHST- 2021/08/30 00:00 [revised]
PHST- 2021/10/22 00:00 [accepted]
PHST- 2022/01/14 06:09 [entrez]
PHST- 2022/01/15 06:00 [pubmed]
PHST- 2022/03/04 06:00 [medline]
PHST- 2021/12/21 00:00 [pmc-release]
AID - S2666-3791(21)00323-2 [pii]
AID - 100455 [pii]
AID - 10.1016/j.xcrm.2021.100455 [doi]
PST - epublish
SO  - Cell Rep Med. 2021 Dec 21;2(12):100455. doi: 10.1016/j.xcrm.2021.100455. 
      eCollection 2021 Dec 21.