Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer.

Autor: Miller AM; Department of Surgery, University of Iowa Hospitals and Clinics, University of Iowa, Iowa City, IA, USA., Lemke-Miltner CD; Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Blackwell S; Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Tomanek-Chalkley A; Department of Surgery, University of Iowa Hospitals and Clinics, University of Iowa, Iowa City, IA, USA., Gibson-Corely KN; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.; Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Coleman KL; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Weiner GJ; Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Chan CHF; Department of Surgery, University of Iowa Hospitals and Clinics, University of Iowa, Iowa City, IA, USA. carloshfchan@gmail.com.; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA. carloshfchan@gmail.com.
Jazyk: angličtina
Zdroj: Annals of surgical oncology [Ann Surg Oncol] 2021 Feb; Vol. 28 (2), pp. 1187-1197. Date of Electronic Publication: 2020 May 14.
DOI: 10.1245/s10434-020-08591-7
Abstrakt: 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.
Databáze: MEDLINE
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