Cowpea mosaic virus (CPMV) promotes antitumor activity and immunological memory in an ovarian tumor model

Ovarian cancer is one of the main causes of mortality among women, often diagnosed in advanced stages with tumors disseminated in the peritoneal cavity. Immunotherapy has shown benefits in solid tumors, including ovarian cancer. Cowpea Mosaic Virus (CPMV) is a promising plant virus for use in immunotherapy due to its immunostimulatory properties and inability to infect humans. This study aimed to review the current literature on the use of CPMV in ovarian cancer models. A search was carried out in the PUBMED database in July 2024 using the descriptors “Ovarian Cancer” and “Cowpea Mosaic Virus”. Articles published in the last five years that evaluated the effectiveness of CPMV were included. The results show that weekly intraperitoneal (IP) treatment with the CPMV vaccine in situ significantly delayed tumor growth, improved survival, and prevented recurrence in murine models of ovarian cancer. Injection of CPMV into cancerous tissue induced a potent immune response, converting immunosuppressive neutrophils into pro-inflammatory ones, which killed tumor cells and recruited dendritic cells, T cells, and NK cells to the tumor site. This resulted in the induction of costimulatory molecules in CD11b myeloid cells and the upregulation of interleukin-6 and interferon-γ, in addition to the downregulation of IL-10 and TGF-β, associated with the activation of macrophages and neutrophils to an antitumor phenotype. Conversion of immunosuppressive myeloid cells into potent antigen-presenting cells significantly improved effector and memory CD4+ and CD8+ T cell responses by promoting the cytotoxic activity of systemic tumor-specific CD8+ T cells. Combining in situ vaccination with immune checkpoint therapy generated tumor-specific immune responses and lasting protection against relapse. When CPMV was conjugated to a polymer, prolonged immunological stimulation was observed, likely due to the continued presence of CPMV in the IP space. These findings suggest that the therapeutic effects achieved by in situ CPMV vaccination can be harnessed to potentiate systemic antitumor immunity, providing a robust rationale for CPMV clinical trials.

Corresponding author: Renata Kelly de Freitas Mano (e-mail: renata.mano@aluno.uece.br).