Combination of cowpea mosaic virus (CPMV) intratumoral therapy and oxaliplatin chemotherapy†
Abstract
Cowpea mosaic virus is a potent intratumoral immunotherapy agent that has shown promise in preclinical studies and canine cancer trials with tumor- and tissue-agnostic efficacy. As we move towards the clinic, it is imperative to investigate combination strategies that synergize to further improve the potency of the approach. Here, we combined CPMV with the clinically approved chemotherapeutic agent oxaliplatin. CPMV's ability to recruit and activate naive immune cells synergized with oxaliplatin's ability to induce immunogenic cell death in the ID8-Defb29/Vegf-A ovarian and B16F10 melanoma murine cancer models with an increase of median survival of 57.7% and 162.2%, respectively. The combination therapy outperformed the CPMV or oxaliplatin monotherapy, and achieved a percent difference in tumor burden of 26.1% and 170.6% in the ID8-Defb29/Vegf-A ovarian and B16F10 melanoma models, respectively. Immunofluorescence staining of treated tumor sections elucidated the role of damage associated molecular patterns (calreticulin and HMGB1), innate immune cells (myeloid cells – likely neutrophils, NK cells, and macrophages), and regulatory T cells (Tregs) as a function of the treatment regimen. Overall, our proposed combination therapy modulated the dormant tumor microenvironment which resulted in effective tumor cell death. This study demonstrates the potential for clinical combination of chemotherapy and CPMV intratumoral immunotherapy.