Grant: Project Grant

Lymph node metastasis (LNM) is a common and serious complication in many cancers, such as melanoma breast cancer, and lung cancer. Current treatments such as surgery, radiation, and systemic therapies often fail to completely eliminate LNMs leading to disease recurrence. As a result, there is a pressing need for alternative strategies to effectively treat LNMs. The immune environment within LNMs, like many tumors, is immunosuppressive, which hinders the body's natural ability to fight cancer. While much research has focused on improving cancer immunotherapy by targeting the tumor microenvironment, little attention has been given to reprogramming the immune environment within LNMs. Recent evidence, including our own preliminary findings, has identified a unique, reductive extracellular environment in LNMs characterized by elevated glutathione (GSH) levels. We propose that this distinct environment can be exploited for targeted immunotherapy. Our goal is to develop a GSH-responsive nanocomplex that can deliver immunomodulatory treatments specifically to LNMs, thereby enhancing anti-LNM immune responses while avoiding unnecessary immune activation in healthy tissues. We will evaluate the anti-tumor efficacy of nanocomplex in various mouse models, and examine the biosafety of nanocomplex treatment. Through this research, we aim to establish a new paradigm in cancer treatment that could transform LNMs into hubs for durable anti-tumor immunity, offering a promising alternative to existing therapies and addressing critical unmet needs in cancer care.