Our project uses an unconventional approach to cancer treatment by in situ vaccines (ISVs) application as a form of therapeutic vaccination strategy. By delivering proinflammatory mediators and immunostimulatory agents, we aim to overcome the immunosuppressive tumor microenvironment. Through the application of ISVs, we bypass the need for tumor-specific antigen identification and vaccine design, instead promoting the release of tumor antigens and enhancing T cell responses. Mucosal delivery allows targeting the tumor site directly, thus boost local immune responses while minimizing systemic side effects. We will evaluate the efficacy of CpG-Tat as a mucosal ISV in an in vivo orthotopic lung cancer model, which is the more accurate representation of human lung cancer in terms of the tumor environment, growth patterns, and response to therapies. This approach, if successful, holds a great potential to revolutionize cancer treatment by increasing treatment efficacy, limiting toxicity, and introducing a non-invasive, patient-friendly platform that could significantly improve the life quality of patients.