The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.
1 December 2018 in Journal of Cranio-Maxillofacial Surgery
Oral cancer is one of the most common tumours in the world threatening human life and health. The 5-years survival rate of patients with oral cancer has not been improved significantly for many years. The existing clinical diagnostic methods rarely achieve early diagnosis due to deficiencies such as lack of sensitivity. Most of the patients have progressed to the advanced stages when oral cancer is detected. Unfortunately, the traditional treatment methods are usually ineffective at this stage. Therefore, there is an urgent need for more effective and precise techniques for early diagnosis and effective treatment of oral cancer. In recent decades, nanomedicine has been a novel diagnostic and therapeutic platform for various diseases, especially cancer. The synthesis and application of various nanoagents have emerged at the right moment. Among them, polymer nanoagents have unique advantages, such as good stability, high biosafety and high drug loading, showing great potential in the early accurate diagnosis and treatment of tumours. In this review, we focus on the application of advanced polymeric nanoagents in both the diagnosis and treatment of oral cancer. Then, the future therapy strategies and trends for polymeric nanoagents applied to oral cancer are discussed, with the hope that more advanced nanomedical technology will be applied to oral cancer research and promote the development of stomatology.