Metastatic Colon Cancer Treatment Using S100A9-Targeted Cowpea Mosaic Virus Nanoparticles

Abstract

Peritoneal metastases (PMs) occur due to the metastasis of gynecological and gastrointestinal cancers such as ovarian, colon, pancreatic, or gastric tumors. PM outgrowth is often fatal, and patients with PMs have a median survival of 6 months. Cowpea mosaic virus (CPMV) has been shown, when injected intratumorally, to act as an immunomodulator reversing the immunosuppressive tumor microenvironment, therefore turning cold tumors hot and priming systemic antitumor immunity. However, not all tumors are injectable, and PMs especially will require targeted treatments to direct CPMV toward the disseminated tumor nodules. Toward this goal, we designed and tested a CPMV nanoparticle targeted to S100A9, a key immune mediator for many cancer types indicated in cancer growth, invasiveness, and metastasis. Here, we chose to use an intraperitoneal (IP) colon cancer model, and analysis of IP gavage fluid demonstrates that S100A9 is upregulated following IP challenge. S100A9-targeted CPMV particles displaying peptide ligands specific for S100A9 homed to IP-disseminated tumors, and treatment led to improved survival and decreased tumor burden. Targeting CPMV to S100A9 improves preclinical outcomes and harbors the potential of utilizing CPMV for the treatment of IP-disseminated diseases.

Prognostic Biomarkers for Hepatocellular Carcinoma Based on Serine and Glycine Metabolism-related Genes

“…33,34 S100A9 is a widely studied biomarker in recent years and a pivotal mediator of cancer progression. [35][36][37] It is worth noting that clinical studies have found that downregulation of S100A9 expression in HCC can significantly inhibit cancer cell growth. 38 Therefore, targeting S100A9 is a possible strategy for HCC patients.…”

Progress in the Treatment of Peritoneal Metastatic Cancer and the Application of Therapeutic Nanoagents

“…With ), and the CPMV capsid was modified with peptides to extend the ability of CPMV. 193 CPMV is a plant small ribonucleic acid virus that has been explored as an immunomodulatory agent for cancer therapy via in situ vaccination. The H6 and G3 used for modification bind to S100A9 molecules overexpressed in a variety of cancers including breast, ovarian, pancreatic, and gastric cancers for systemic administration of targeted therapies.…”

“…Copyright 2022, American Chemical Society. (b) Intratumoral injection of CPMV acts as an immunomodulator, reverses the immunosuppressive tumor microenvironment, warms up cold tumors, and induces systemic antitumor immunity . Reproduced from ref .…”

“…It triggered a strong innate and adaptive immune response within the peritoneal tumor microenvironment in a mouse animal model, thereby enhancing the efficacy of immune checkpoint inhibitors in immunotherapy-resistant kidney and breast cancers. In contrast to the above genetically engineered viruses, Chung et al reported a cowpea mosaic virus (CPMV) modified with peptides (called H6 and G3), and the CPMV capsid was modified with peptides to extend the ability of CPMV . CPMV is a plant small ribonucleic acid virus that has been explored as an immunomodulatory agent for cancer therapy via in situ vaccination.…”

“…In contrast, the prepared NK4 binds to the c-Met/HGF receptor, does not induce tyrosine phosphorylation of c-Met, and has an inhibitory effect on the angiogenic pathway driven by basic fibroblast growth factor and vascular endothelial growth factor, all of which suggest that this gene therapy may be an ideal regimen for the treatment of peritoneal metastatic cancer. With 193 CPMV is a plant small ribonucleic acid virus that has been explored as an immunomodulatory agent for cancer therapy via in situ vaccination. The H6 and G3 used for modification bind to S100A9 molecules overexpressed in a variety of cancers including breast, ovarian, pancreatic, and gastric cancers for systemic administration of targeted therapies.…”