Journal article
Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer
Annals of surgical oncology, Vol.28(2), pp.1187-1197
02/01/2021
DOI: 10.1245/s10434-020-08591-7
PMCID: PMC7666039
PMID: 32409965
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 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.
Details
- Title: Subtitle
- Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer
- Creators
- Ann M Miller - University of IowaCaitlin D. Lemke-Miltner - University of IowaSue Blackwell - University of IowaAnn Tomanek-Chalkley - University of IowaKatherine N. Gibson-Corely - University of Iowa Hospitals and ClinicsKristen L. Coleman - University of IowaGeorge J. Weiner - University of IowaCarlos H. F. Chan - University of Iowa Hospitals and Clinics
- Resource Type
- Journal article
- Publication Details
- Annals of surgical oncology, Vol.28(2), pp.1187-1197
- DOI
- 10.1245/s10434-020-08591-7
- PMID
- 32409965
- PMCID
- PMC7666039
- NLM abbreviation
- Ann Surg Oncol
- ISSN
- 1068-9265
- eISSN
- 1534-4681
- Publisher
- Springer Nature
- Number of pages
- 11
- Grant note
- P30 CA086862 / National Cancer Institute of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Holden Comprehensive Cancer Center T32 CA078586 / National Institutes of Health Free Radical and Radiation Biology; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 02/01/2021
- Academic Unit
- Microbiology and Immunology; Hematology, Oncology, and Blood & Marrow Transplantation; The University of Iowa Institute for Vision Research; Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Radiation Oncology; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984312969402771
Metrics
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