Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancer

Mayo Clinic Rochester, Rochester MN

Investigators

Linked publications & trials

Abstract

ABSTRACT High-grade serous ovarian carcinoma (HGSOC) is the most common and lethal subtype of ovarian cancer with a median 5-year survival rate of ~20%. 70-95% of patients with late-stage HGSOC recur or progress with current chemotherapeutic regimens making HGSOC the leading cause of gynecological cancer-related deaths in the developed world. Immunotherapy approaches, including immune checkpoint blockade (ICB ), have also had only limited success for treating HGSOC. This motivates the need to develop novel chemotherapies and immuno- therapies for treating ovarian cancer. This goal is being pursued by the Ovarian Cancer SPORE (P50) at Mayo Clinic. The SPORE consists of three research projects and four cores. The latter include Biospecimens and Patient Registry (Core B) and Animal Models (Core D). In Project 2, the SPORE is seeking to assess efficacy of a novel chemotherapy agent, topoisomerase 1 inhibitor (TOP1i), for treating PARPi and platinum-resistant disease. In Project 4, the SPORE members are developing NK-cells genetically engineered for enhanced per- sistence and target specificity. For preclinical testing, both projects rely heavily on the Animal Models Core, focusing on patient derived xenograft (PDX) mouse models of HGSOC. While incredibly useful, mouse models have significant challenges that include high cost, limited throughput and lack of human tumor microenvironment (TME). The objective of our competitive revision project is to implement novel IMAT-funded microfluidic cancer cultures for preclinical and clinical testing within the Ovarian Cancer SPORE at Mayo Clinic. The Revzin lab has devel- oped microfluidic devices for culturing: 1) patient-derived organoids and 2) tumor explants. Like PDX mice, our microfluidic cancer cultures utilize patient tissue but offer benefits of simplicity, lower cost and much shorter turnaround time. Microfluidic tumor explant cultures have the additional benefit of preserving patient-specific TME, complete with immune and stromal cell compartments. In this project, our team will test the hypothesis that microfluidic cancer cultures serve as an enabling technology for assessing the efficacy of novel ovarian cancer therapies and as companion diagnostics for clinical trials run by the Ovarian Cancer SPORE. Impact: This competitive revision project represents a unique opportunity to incorporate recently developed, IMAT-funded microfluidic cancer cultures into Phase I clinical trials of ovarian cancer therapies. Successful com- pletion of this project will establish the utility of our cancer culture devices as companion diagnostics, enable potential Phase II trials, and pave the way for commercialization of this exciting technology.