Enhanced Antitumor Efficacy of Oncolytic Vaccinia Virus Therapy Through Keratin-Mediated Delivery in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) represents an aggressive subtype characterized by high rates of recurrence and metastasis, necessitating the exploration of alternative treatment strategies. Oncolytic vaccinia virus (OVV) therapy has emerged as a promising approach, selectively infecting and destroying tumor cells. However, its efficacy is often hampered by inadequate viral distribution within the tumor microenvironment. Here, we investigate the potential of keratin (KTN) as a carrier for OVV delivery to enhance viral distribution and antitumor efficacy. In vitro assays revealed that KTN significantly improves OVV stability, leading to increased tumor cell apoptosis and necrosis. Furthermore, KTN effectively inhibits cancer cell migration by suppressing the epithelial-mesenchymal transition (EMT) process and downregulating metastasis-related proteins. These findings are corroborated in a syngeneic TNBC mouse model, where KTN-mediated OVV delivery enhances cytotoxic T cell-mediated antitumor immune responses without compromising the anti-angiogenic effects of the virus. Notably, KTN alone exhibits antitumor effects by suppressing tumor growth and metastasis, underscoring its potential as a standalone therapeutic agent. In conclusion, our study underscores the promise of KTN-mediated OVV delivery as a promising therapeutic strategy for TNBC. By improving viral distribution, suppressing EMT, and enhancing antitumor immunity, this approach holds significant potential for enhancing patient outcomes in TNBC treatment. Further investigation is warranted to explore the broader utility of KTN in various cancer therapy approaches.