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Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer
- Source :
- Ann Surg Oncol
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- 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 Qβ bacteriophage capsid protein encapsulating a CpG-A oligodeoxynucleotide, activates plasmacytoid dendritic cells (pDCs) and triggers interferon alpha (IFNα) 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 IFNα 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 IFNα (range, 0–4700 pg/ml; n = 14). The IFNα 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-1β), pro-inflammatory cytokines (IFNγ, 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.
- Subjects :
- Chemokine
medicine.medical_treatment
030230 surgery
Article
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
In vivo
Cytidine Monophosphate
Tumor Microenvironment
Animals
Humans
Medicine
Peritoneal Neoplasms
Tumor microenvironment
biology
business.industry
Dendritic Cells
Immunotherapy
Interleukin-12
Oncology
030220 oncology & carcinogenesis
Interleukin 12
Cancer research
biology.protein
Cytokines
Surgery
business
Ex vivo
CD8
Subjects
Details
- ISSN :
- 15344681 and 10689265
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Annals of Surgical Oncology
- Accession number :
- edsair.doi.dedup.....899961b5cd75f55d02e51672da2129d0