Journal
ANNALS OF SURGICAL ONCOLOGY
Volume 28, Issue 2, Pages 1187-1197Publisher
SPRINGER
DOI: 10.1245/s10434-020-08591-7
Keywords
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Funding
- Holden Comprehensive Cancer Center
- National Cancer Institute of the National Institutes of Health [P30 CA086862]
- National Institutes of Health Free Radical and Radiation Biology [T32 CA078586]
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The novel immunotherapeutic agent, CMP-001, composed of bacteriophage capsid protein and CpG-A oligodeoxynucleotide, activates pDCs and triggers IFN alpha release, leading to anti-tumor immune effects. In vitro stimulation with CMP-001 showed IFN alpha release and increased percentage of pDCs in peritoneal cells. In vivo studies in murine PC models demonstrated improved survival and enhanced immune response with CMP-001 treatment.
Background The treatment options for patients with peritoneal carcinomatosis (PC) of gastrointestinal and pancreaticobiliary origins are limited. The virus-like particle, CMP-001, composed of the Q beta bacteriophage capsid protein encapsulating a CpG-A oligodeoxynucleotide, activates plasmacytoid dendritic cells (pDCs) and triggers interferon alpha (IFN alpha) release, leading to a cascade of anti-tumor immune effects. Methods To evaluate the ability of CMP-001 to trigger an immune response in patients with PC, peritoneal cells were isolated and stimulated ex vivo with CMP-001. Both IFN alpha release and percentage of pDC were quantified using enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. To evaluate the anti-tumor response in vivo, murine PC models were generated using mouse cancer cell lines (Panc02 and MC38) in immunocompetent mice treated with intraperitoneal CMP-001 or saline control. Survival was followed, and the immunophenotype of cells in the peritoneal tumor microenvironment was evaluated. Results The pDCs accounted for 1% (range 0.1-3.9%; n = 17) of the isolated peritoneal cells. Ex vivo CMP-001 stimulation of the peritoneal cells released an average of 0.77 ng/ml of IFN alpha (range, 0-4700 pg/ml; n = 14). The IFN alpha concentration was proportional to the percentage of pDCs present in the peritoneal cell mixture (r = 0.6; p = 0.037). In murine PC models, intraperitoneal CMP-001 treatment elicited an anti-tumor immune response including an increase in chemokines (RANTES and MIP-1 beta), pro-inflammatory cytokines (IFN gamma, interleukin 6 [IL-6], and IL-12), and peritoneal/tumor immune infiltration (CD4(+)/CD8(+) T and natural killer [NK] cells). The CMP-001 treatment improved survival in both the Panc02 (median, 35 vs 28 days) and the MC38 (median: 57 vs 35 days) PC models (p < 0.05). Conclusions As a novel immunotherapeutic agent, CMP-001 may be effective for treating patients with PC.
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