LAUSR

Peritoneal carcinomatosis is a common form of metastasis occurring in approximately 10% of gastrointestinal and pancreatic cancers with life expectancy often less than 6-12 months. Due to the limited options for treatment of peritoneal carcinomatosis, there is a significant need for novel therapeutic strategies. We explored the therapeutic potential of CMP-001, a novel virus-like particle composed of the Qβ bacteriophage capsid protein encapsulating an immunostimulatory CpG-A oligodeoxynucleotide (CpG-A ODN) in this cancer. CpG-A ODN is a known activator of toll-like receptor 9 (TLR9), which is expressed by human and murine plasmacytoid dendritic cells (pDCs). Initial studies evaluated the effect of CMP-001 in vitro on cells obtained from the ascitic fluid of patients with peritoneal carcinomatosis. These studies demonstrated that pDCs are present in the ascitic fluid and produce IFN-α in response to CMP-001 stimulation. A mouse model of peritoneal carcinomatosis was used to further explore the therapeutic potential of CMP-001. C57BL/6 mice were challenged intraperitoneally (i.p.) with Panc02 mouse pancreatic cancer cells. On days 5, 9, and 13 post-tumor challenge mice were treated i.p. with either saline or 100 μg CMP-001. Mice treated with CMP-001 had a median survival of 35 days compared to mice treated with saline alone with a median survival of 28 days (n = 10 per group, p = 0.028). Examination of the immune response demonstrated CMP-001 induced an influx of dendritic cells (CMP- 001 8.99% ± 0.95 vs saline 4.57% ± 0.7, p = 0.0015), NK cells (CMP-001 0.26% ± 0.052 vs saline 0.087% ± 0.0085, p = 0.006), and CD4+ T cells (CMP-001 3.29% ± 0.85 vs saline 0.95% ± 0.097, p = 0.0168) into the ascitic fluid. In addition, CMP-001 induced a significant increase in antigen-experienced, effector and memory, CD11ahiCD44hi CD4+ T cells (CMP-001 54.55% ± 6.52 vs saline 28.12% ± 3.68, p = 0.0028) and CD11ahiCD8αlo CD8+ T cells (CMP-001 58.49% ± 4.47 vs saline 23.04% ± 2.86, p Citation Format: Ann M. Miller, Caitlin Lemke-Miltner, Sue Blackwell, Ann Tomanek-Chalkley, Kristen Coleman, George Weiner, Carlos Chan. CMP-001, a virus-like particle containing immunostimulatory CpG-A, for treatment of peritoneal carcinomatosis of gastrointestinal and pancreatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3273.