Tumor draining lymphatics and regional the lymph nodes play important roles in cancer metastases and cancer immunotherapies. In patients with locally advanced cancers, “naïve” T-cells within the tumor draining LNs are prevented from becoming “educated” to attack cancer by a series of “checkpoints”. Therapeutics to block these checkpoints are typically given intravenously -- which is an ineffective means to maximize drug in the tumor draining LNs. While effective, a dangerous side effect of these i.v. administered therapeutics is that the entire immune system can become overstimulated, attacking normal tissues as well as tumors. In fact, the immune-related adverse effects (irAEs) can be s...
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Tumor draining lymphatics and regional the lymph nodes play important roles in cancer metastases and cancer immunotherapies. In patients with locally advanced cancers, “naïve” T-cells within the tumor draining LNs are prevented from becoming “educated” to attack cancer by a series of “checkpoints”. Therapeutics to block these checkpoints are typically given intravenously -- which is an ineffective means to maximize drug in the tumor draining LNs. While effective, a dangerous side effect of these i.v. administered therapeutics is that the entire immune system can become overstimulated, attacking normal tissues as well as tumors. In fact, the immune-related adverse effects (irAEs) can be severe and limit the efficacy of currently approved immunotherapies as well as emerging immunotherapies. We believe that irAEs can be alleviated by administering these therapeutics directly into the lymphatics feeding the tumor draining lymph nodes rather than intravenously. Unfortunately, there has been no method available to deliver therapeutic doses directly into the lymphatics in animal models or in humans. Herein we seek to validate a nanotechnology/ nanotopography infusion device in a preclinical melanoma model of lymph node metastases to show lymphatic delivery of checkpoint inhibitors can concentrate drug within the regional lymphatics and improve tumor response. Next, in a pilot study in melanoma patients, we plan to demonstrate that the infusion device can deliver sufficient volumes of fluid needed for therapeutic dosing of checkpoint blockade inhibitors in patients with locally advanced melanoma. This project is designed to mimic the planned clinical implementation in Dr. Hwu’s melanoma clinic at MD Anderson, and if successful, could hasten the translation of other emerging immunotherapies.
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