I-Corps: Translation Potential of Intratumoral Drug Delivery System

The broader impact of this I-Corps project is the development of image-guided therapy for local injection into tumors ("intratumoral") to treat immunotherapy-resistant solid cancers. Treatment for such diseases constitutes a $125 billion market. Currently, the only approved intratumoral therapy costs $65,000-100,000/patient and is reimbursed by insurance. Through early findings, it was identified that pharmaceutical companies with immune-oncology therapeutics are interested in strategic partnerships and acquisitions to improve the delivery of their drugs. Intravenous or oral medications struggle with toxicity and efficacy issues, motivating pharmaceutical companies to partner with intratumoral drug delivery technologies. Current intratumoral approaches are limited by rapid drug leakage out of the tumor (>70% has dissipated within hours) as well as the need for frequent, impractical repeat doses (clinical workflow only allows monthly dosing or less). Initial discussions with pharmaceutical heads of immune oncology departments and physicians running clinical trials indicates stage IV, Microsatellite instability (MSI)-low colorectal cancer with metastases to the liver is a strong clinical need and potential initial market, with additional interest in pancreatic, lung, and triple-negative breast cancer. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. This solution is based on the development of a local, sustained intratumoral drug delivery system to create a "cancer vaccine." By modifying the local tumor microenvironment, this technology educates the immune system to fight cancer locally and at distant metastatic sites (the "abscopal effect") with minimal toxicity risk. Current intratumoral drug delivery methods have failed due to rapid drug leakage, difficulty in visualizing the drug upon intratumoral injection, and insufficient drug persistence for a sustained immune response. This solution addresses these issues with an injectable drug delivery platform that delivers a high payload of an immune-activating drug into a tumor, which then which solidifies at body temperature to keep the drug in the tumor for sustained release with low therapeutic leakage. The technology also includes a low dose of an imaging agent to ensure accurate placement. This therapy creates a sustained immune response against traditionally immunotherapy-resistant solid tumors, resulting in the destruction of tumors locally and at untreated metastatic sites with high rates of complete regression in 90-day survival studies. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.