Journal article
Antibody Opsonization of a TLR9 Agonist-Containing Virus-like Particle Enhances In Situ Immunization
The Journal of immunology (1950), Vol.204(5), pp.1386-1394
03/01/2020
DOI: 10.4049/jimmunol.1900742
PMCID: PMC7033003
PMID: 31953355
Abstract
The immunologic and therapeutic effects of intratumoral (IT) delivery of a novel virus-like particle as a lymphoma immunotherapy were evaluated in preclinical studies with human cells and a murine model. CMP-001 is a virus-like particle composed of the Qβ bacteriophage capsid protein encapsulating an immunostimulatory CpG-A oligodeoxynucleotide TLR9 agonist. In vitro, CMP-001 induced cytokine production, including IFN-α from plasmacytoid dendritic cells, but only in the presence of anti-Qβ Ab. In vivo, IT CMP-001 treatment of murine A20 lymphoma enhanced survival and reduced growth of both injected and contralateral noninjected tumors in a manner dependent on both the ability of mice to generate anti-Qβ Ab and the presence of T cells. The combination of IT CMP-001 with systemic anti-PD-1 enhanced antitumor responses in both injected and noninjected tumors. IT CMP-001 alone or combined with anti-PD-1 augmented T cell infiltration in tumor-draining lymph nodes. We conclude IT CMP-001 induces a robust antitumor T cell response in an anti-Qβ Ab-dependent manner and results in systemic antitumor T cell effects that are enhanced by anti-PD-1 in a mouse model of B cell lymphoma. Early-phase clinical evaluation of CMP-001 and anti-PD-1 combination therapy in lymphoma will begin shortly, based in part on these results.
Details
- Title: Subtitle
- Antibody Opsonization of a TLR9 Agonist-Containing Virus-like Particle Enhances In Situ Immunization
- Creators
- Caitlin D Lemke-Miltner - University of IowaSue E Blackwell - University of IowaChaobo Yin - University of IowaAnna E Krug - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242;Aaron J Morris - Checkmate Pharmaceuticals, Cambridge, MA 02142; and.Arthur M Krieg - Checkmate Pharmaceuticals, Cambridge, MA 02142; and.George J Weiner - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242;
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.204(5), pp.1386-1394
- DOI
- 10.4049/jimmunol.1900742
- PMID
- 31953355
- PMCID
- PMC7033003
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- P30 ES005605 / NIEHS NIH HHS S10 RR025439 / NCRR NIH HHS P30 CA086862 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
- Language
- English
- Date published
- 03/01/2020
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984359699702771
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