Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer.
Journal
Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
04
03
2020
pubmed:
16
5
2020
medline:
28
4
2021
entrez:
16
5
2020
Statut:
ppublish
Résumé
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. 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. 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 As a novel immunotherapeutic agent, CMP-001 may be effective for treating patients with PC.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
CONCLUSIONS
As a novel immunotherapeutic agent, CMP-001 may be effective for treating patients with PC.
Identifiants
pubmed: 32409965
doi: 10.1245/s10434-020-08591-7
pii: 10.1245/s10434-020-08591-7
pmc: PMC7666039
mid: NIHMS1634169
doi:
Substances chimiques
Cytokines
0
Interleukin-12
187348-17-0
Cytidine Monophosphate
F469818O25
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1187-1197Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES005605
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA086862
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA078586
Pays : United States
Organisme : Holden Comprehensive Cancer Center, University of Iowa
ID : Mezhir Awards for Collaborative Research
Organisme : NIH HHS
ID : T32 CA078586
Pays : United States
Organisme : NIH HHS
ID : T32 CA078586
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA086862
Pays : United States
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