Abstract
The current study investigates the use of an immunostimulatory plant virus nanoparticle called the cowpea mosaic virus (CPMV) in both the prophylaxis and treatment of metastatic breast cancer and melanoma. Metastatic cancer remains to this day one of the most difficult areas in oncology to treat and diagnose. Current standardized treatments consist of systemically administered chemotherapeutics, which are not targeted to the diseased areas and oftentimes cause significant side effects. Therefore, novel treatments such as targeted immunotherapies are under development. The S100A9 protein is upregulated in the tumor microenvironment and it plays an important role in tumor metastasis, aggressiveness, and tumor immunosuppression. It is present not only in the pre-metastatic tumor environment, but is also heavily secreted and expressed after metastatic tumor establishment has occurred. This makes S100A9 a prime target in both prophylactic and therapeutic settings; yet, targeted immunotherapies against S100A9 have never previously been explored. CPMV has been shown in the past to be immunostimulatory when injected directly into the tumor with the ability to recruit immune cells for tumor cell killing. However, metastatic tumors cannot be treated through intratumoral injections; therefore, the current work utilizes systemically-administered S100A9-targeted CPMV nanoparticles. Biodistribution studies indicate that S100A9-targeted CPMV homes to the lung while confocal imaging of S100A9 and S100A9-targeted CPMV within the lungs of tumor-inoculated mice demonstrates co-localization. We further demonstrate using flow cytometry that after CPMV homes to the lungs, immune cells such as neutrophils and dendritic cells are recruited to the lungs, and macrophages are polarized towards their antitumor M1 phenotype. Prophylaxis efficacy studies where CPMV is injected before the tumors show that the S100A9-targeted CPMV causes tumor rejection in both metastatic breast cancer and melanoma but that native CPMV does not produce a significant effect. When used as a treatment, the targeted CPMV, similarly shows efficacy against these two cancer models with native CPMV again showing ineffectiveness. The S100A9-targeted CPMV holds great potential as a targeted immunotherapy both prophylactically (e.g. after primary tumor debulking to reduce the onset of metastases) and therapeutically after tumor establishment has occurred.
Citation Format: Young Hun Chung, Jooneon Park, Hui Cai, Nicole F. Steinmetz. Prophylaxis and treatment of metastatic breast cancer and melanoma using S100A9-targeted cowpea mosaic virus nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 297.
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