Monocytes Exposed to Immune Complexes Reduce pDC Type 1 Interferon Response to Vidutolimod

Shakoora A. Sabree; Caitlin D. Lemke-Miltner; Sue E. Blackwell; Chaobo Yin; Aaron Bossler; Kareem Ebeid; Aliasger K. Salem; George J. Weiner

doi:10.3390/vaccines9090982

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Monocytes Exposed to Immune Complexes Reduce pDC Type 1 Interferon Response to Vidutolimod

Journal article

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Monocytes Exposed to Immune Complexes Reduce pDC Type 1 Interferon Response to Vidutolimod

Shakoora A. Sabree, Caitlin D. Lemke-Miltner, Sue E. Blackwell, Chaobo Yin, Aaron Bossler, Kareem Ebeid, Aliasger K. Salem and George J. Weiner

Vaccines (Basel), Vol.9(982), p.982

09/01/2021

DOI: 10.3390/vaccines9090982

PMCID: PMC8473335

PMID: 34579220

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Abstract

Vidutolimod, also known as CMP-001, is a virus-like particle composed of the Qβ bacteriophage coat protein encasing a TLR9 agonist. Vidutolimod injected intratumorally is showing promise in early phase clinical trials based on its ability to alter the tumor microenvironment and induce an anti-tumor immune response. We previously demonstrated that the in vivo efficacy of vidutolimod is dependent on the presence of anti-Qβ antibodies that enhance opsonization and uptake of vidutolimod by TLR9-expressing plasmacytoid dendritic cells (pDCs). Here, we evaluated the effect of immune complexes, including anti-Qβ-coated vidutolimod, on induction of Type 1 Interferon production by peripheral blood mononuclear cells in response to vidutolimod and soluble TLR9 agonists. Immune complexes, including but not limited to anti-Qβ-coated vidutolimod, indirectly suppressed TLR9-mediated Type 1 Interferon production by pDCs in a monocyte-dependent manner. These findings indicate that anti-Qβ-coated vidutolimod has effects in addition to those mediated by TLR9 that could have important clinical implications for understanding the mechanism of action of this exciting new approach to in situ immunization and cancer immunotherapy.

Fc gamma receptor

monocytes

pDCs

TLR9

Type 1 Interferon

vidutolimod

Details

Title: Subtitle: Monocytes Exposed to Immune Complexes Reduce pDC Type 1 Interferon Response to Vidutolimod
Creators: Shakoora A. Sabree - University of Iowa
Caitlin D. Lemke-Miltner - University of Iowa
Sue E. Blackwell - University of Iowa
Chaobo Yin - University of Iowa
Aaron Bossler - University of Iowa Hospitals and Clinics
Kareem Ebeid - University of Iowa
Aliasger K. Salem - University of Iowa
George J. Weiner - University of Iowa
Resource Type: Journal article
Publication Details: Vaccines (Basel), Vol.9(982), p.982
DOI: 10.3390/vaccines9090982
PMID: 34579220
PMCID: PMC8473335
NLM abbreviation: Vaccines (Basel)
ISSN: 2076-393X
eISSN: 2076-393X
Publisher: MDPI AG
Language: English
Date published: 09/01/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9984183997502771

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