PDT-NEO-immunother · Generation of tumor neoantigens with photodynamic therapy: a new strategy for anticancer vaccines to fight head and neck cancer

Generation of tumor neoantigens with photodynamic therapy: a new strategy for anticancer vaccines to fight head and neck cancer

Head and neck squamous cell carcinomas (HNSCC) represent a major global health challenge, ranking among the most common cancers in men, with nearly 900,000 new cases and 450,000 deaths annually worldwide. Despite advances in treatment, including surgery combined with radiotherapy or chemotherapy, outcomes for patients with advanced disease remain poor, with treatment failure occurring in up to 40% of cases. This highlights a critical unmet need for more effective and durable therapeutic strategies capable of overcoming tumor resistance and preventing relapse. In this context, there is growing interest in the development of more selective and personalized cancer therapies that specifically target tumor cells while minimizing toxicity to healthy tissues. One promising approach is immunotherapy, which works by helping the body’s own immune system recognize and attack cancer. This approach can be even more effective when combined with treatments that actively stimulate immune responses against tumors. An important concept in this field is immunogenic cell death (ICD). This is a special type of cancer cell death that not only destroys tumor cells but also activates the immune system. ICD works through two key components. First, it provides adjuvanticity, meaning that dying cancer cells release “danger signals” that alert and stimulate the immune system. Second, it provides antigenicity, meaning that cancer cells carry specific markers (antigens) that the immune system can recognize and target. Both components are essential: the danger signals activate the immune response, while the antigens guide the immune system to specifically recognize and attack cancer cells. While the role of these danger signals is well established, it is still unclear whether ICD also enhances antigenicity, for example, by increasing the amount or diversity of tumor-specific antigens, including newly formed ones during treatment. The overall objective of this project is to investigate whether ICD induction promotes increased antigenicity of tumor cells and to exploit this mechanism for the development of personalized cancer vaccines. To this end, photodynamic therapy (PDT) has been selected as a clinically relevant and controllable method to induce ICD. PDT is a minimally invasive treatment that involves administering a light-sensitive drug (called photosensitizer) that accumulates in tumor cells and is then activated by a specific wavelength of light. This activation produces reactive oxygen species that damage and kill the cancer cells. PDT has demonstrated strong immunogenic potential and offers a unique opportunity to locally trigger tumor cell death while also influencing the immune system. By using PDT as a tool to induce ICD, the project aims to determine how this process reshapes the neoantigen repertoire of cancer cells and whether it can enhance their capacity to stimulate effective anti-tumor immune responses. The project follows a structured pathway to impact. First, it aims to characterize the effects of PDT-induced ICD on both adjuvanticity and antigenicity of HNSCC cells, with a particular focus on understanding how therapy influences the tumor antigen landscape. Importantly, the project explores how different types or combinations of antigens could contribute to more effective immune activation, providing insights that can guide future vaccine design strategies. Finally, the project lays the groundwork for the development of personalized vaccination approaches, including dendritic cell-based and mRNA-based platforms, by identifying promising antigenic targets and defining strategies for their potential use. Beyond HNSCC, this project is expected to generate knowledge and methodologies that are transferable to other tumor types. By establishing a strategy to enhance antigenicity through ICD induction and to identify actionable neoantigens, the project contributes to a broader framework for precision immunotherapy. Its outcomes could therefore have significant implications not only for improving treatment responses and preventing relapse in HNSCC patients, but also for advancing personalized cancer vaccination strategies across oncology. Overall, this project aims to bridge a critical gap in current cancer immunotherapy by linking ICD induction to enhanced antigenicity and vaccine design, setting the foundation for more effective and widely applicable anti-cancer treatments.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз