Enhancing therapeutic efficacy through localized radioimmunotherapy via intratumoral nanofluidic drug-eluting seed

World Health Organization estimated that in 2018 about 12% of women were diagnosed with breast cancer, and 17% of them were found to be triple negative breast cancers. Immunotherapy is currently one of the most appealing and promising cancer treatments. However, conventional systemic administration of immunotherapeutics can often lead to adverse side effects and insufficient anti-tumor immune response. Intratumoral delivery of immunotherapeutics can minimize systemic toxicity, increase tumor exposure, and activate an efficient anti-tumor immune response. We developed a nanofluidic-based device for intratumoral drug delivery named nanofluidic drug-eluting seed (NDES). This device can accomplish the clinical demand for a local and sustained drug delivery system. Furthermore, this administration route of immunotherapeutics can avoid repeated intratumoral injections. Similar to brachytherapy seed insertion, the NDES is intratumorally implanted using a trocar procedure, and offers the clinical advantage of eluting drugs. The NDES utilizes nanochannels to passively control drug release, therefore resulting in sustained drug delivery without the need for pumps or action by clinicians. In this thesis, the NDES was used to intratumorally deliver agonist monoclonal antibody CD40 in the 4T1 orthotopic murine mammary carcinoma model, which reproduce triple negative breast cancer. Furthermore, we tried a combination of NDES-mediated intratumoral release of immunotherapeutics with 8 Gy radiation in order to achieve an enhanced local and systemic anti-tumor immune response and tumor growth inhibition.