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

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgments

This study was supported by the Holden Comprehensive Cancer Center through funds from the “Mezhir Awards for Collaborative Research” and the National Cancer Institute of the National Institutes of Health under award number P30 CA086862 for supporting the Molecular Epidemiology Resource Core and Flow Cytometry Facility. Ann M. Miller was supported by the National Institutes of Health Free Radical and Radiation Biology T32 CA078586 training grant. The investigational agent CMP-001 was kindly provided by Checkmate Pharmaceuticals. The Panc02 and MC38 cells were kind gifts from Dr. Xinhui Wang (Massachusetts General Hospital, MA) and Dr. Lorenzo Ferri (McGIll University, PQ, Canada), respectively.

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Authors and Affiliations

  1. Department of Surgery, University of Iowa Hospitals and Clinics, University of Iowa, Iowa City, IA, USA

    Ann M. Miller PhD, Ann Tomanek-Chalkley BS & Carlos H. F. Chan MD, PhD

  2. Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

    Caitlin D. Lemke-Miltner PhD, Sue Blackwell MS & George J. Weiner MD

  3. Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

    Caitlin D. Lemke-Miltner PhD, Sue Blackwell MS, Katherine N. Gibson-Corely DVM, PhD, Kristen L. Coleman PhD, George J. Weiner MD & Carlos H. F. Chan MD, PhD

  4. Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

    Katherine N. Gibson-Corely DVM, PhD

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  1. Ann M. Miller PhD
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Correspondence to Carlos H. F. Chan MD, PhD.

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Disclosure

Caitlin Lemke-Miltner holds stock options in Checkmate Pharmaceuticals. Sue Blackwell owns stocks and holds stock options in Checkmate Pharmaceuticals. George J. Weiner received research funding from Checkmate Pharmaceuticals, but not for this work. Carlos H. F. Chan received the study compound CMP-001 from Checkmate Pharmaceuticals, but did not receive any research funding for this work.

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Miller, A.M., Lemke-Miltner, C.D., Blackwell, S. et al. Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer. Ann Surg Oncol 28, 1187–1197 (2021). https://doi.org/10.1245/s10434-020-08591-7

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