Oral cancer accounts for approximately 2% of all cancer cases worldwide and early detection and diagnosis remain the key for improved survival. Recent clinical studies from the Hasan lab have demonstrated the efficacy of ALA-based photodynamic therapy (PDT) in the treatment of pre-cancerous and cancerous lesions of the oral cavity. Photodynamic therapy (PDT) is a form of cancer treatment involving the administration of nontoxic molecules, referred to as photosensitizers, to tumor cells, followed by irradiation for destruction of cancerous and precancerous cells. Mechanistically, upon irradiation, the photosensitizer absorbs light and undergoes excitation to a higher energy state, followed by a relaxation to an excited triplet state. The transfer of energy or electrons from the excited triplet state to surrounding biomolecules leads to the formation of reactive molecular species and induces cell death. PDT has shown to be an option for the treatment of therapy-resistant cancers, including those resistant to immunotherapy. This research focuses on the use of PDT using 5-ALA as a pro-photosensitizer for the treatment of established oral cancers. We will work on experimenting and analyzing the efficacy of PDT using ALA photosensitization in Mouse Oral Squamous Cell Carcinoma lines, MOC2 and MOC22, with varying proliferation capacities and immunogenicity. We seek to explore the response of these oral cancer cell lines to 5-ALA mediated PDT, both in vitro and in vivo. The overarching goal of this project will be to establish the potential of PDT in inducing an anti-tumor immune response in immunogenic and non-immunogenic tumors and to determine its potential in the treatment of late-stage oral cavity cancers in combination with immunotherapies. In the future, we hope to transfer our findings into utilizing a low-cost, battery-powered, fiber-coupled PDT system suitable for intraoral light delivery enabled by a smartphone interface and embedded electronics for ease of operation in rural and/or resource-limited settings.