将来自远距离机构的零代次患者肿瘤组织整合到快速离体药物筛选平台中

Access to living patient tumor tissue remains a major barrier to accelerating preclinical drug development and informing clinical care. Over the last decade, we have developed a “New Approach Methodology” platform called Screening Live Cancer Explants (SLiCE), which reproducibly engrafts living, passage-zero patient tumors atop substrates of living tissue. Our streamlined four-day drug screening workflow enables tumor engraftment within one day of resection, drug addition one day post-engraftment, and quantification of tumor survival three days later. This procedure is fast enough to accelerate preclinical workflows and inform clinical decisions while minimizing genetic drift. As we expand use of SLiCE in the preclinical setting, our established protocols for collecting and cryopreserving passage-zero tumor tissue have thus far enabled us to cryopreserve over 150 grams of viable brain tumor tissue in over 700 cryovials from 41 patients for personalized drug sensitivity profiling and preclinical testing. Through an active collaboration between UNC and Labcorp, we have shown that replicate cryopreserved aliquots of tumor samples post-thaw are equivalent by whole-exome sequencing (WES), RNA sequencing, and functional drug response. Still, availability of living, passage-zero patient tumor tissue remains our limiting component to further scaling this assay for broad adoption and impact. To overcome this hurdle, our SLiCE Team at UNC is expanding collection of viable tumor tissue to other groups and institutions. A new collaboration with the Mayfield Clinic has successfully yielded shipment of tumor tissues freshly resected from patients at partnering hospitals to UNC. These tumor specimens were viably maintained throughout overnight shipping at 4C, quantified by live tumor cell metabolism via Presto Blue assay, and have been successfully engrafted on SLiCE, quantified by live tumor cell bioluminescence on Day 4 after seeding, the length of our standard drug screening assay. These data provide our first proof-of-concept evidence that tumors resected from patients at distant institutions can be shipped fresh to UNC for testing on SLiCE. Our goal is to continue receiving 3-4 tumors per month from Mayfield to optimize and refine this process. These efforts position SLiCE as a leading New Approach Methodology to test promising experimental agents and one day guide clinical care using passage-zero patient tumor tissues, including fresh, living tumors shipped from other sites.