CAMBRIDGE, MA—Animal models have long been the standard in drug development and cancer research. Now, a team of engineers has developed a test bed that creates just the right conditions for testing on tumor tissue in real-time. The impact could be significant for cancer researchers and drug developers interested in translating scientific findings into practical clinical applications, such as cancer therapies, sooner.
The team, led by Draper, tested the device, called EVIDENT, to see if they could suppress tumor growth using a type of immunotherapy called immune checkpoint inhibitor (ICI) equally well in a living mouse as on a mouse tumor tissue residing in the EVIDENT device.
ICIs have shown remarkable success against melanoma, non-small-cell lung cancer and Hodgkin’s lymphoma. The new approach is described in the peer-reviewed archival International Journal of Molecular Sciences, written by Jeff Borenstein, Vienna Mott and Cassie Bryan of Draper, John Ho and Julia Schueler of Charles River Laboratories and Daniel Doty and Nathan Moore, both formerly of Draper.
“We found excellent correlations between in vivo syngeneic mouse model and in vitro tumor biopsy responses to checkpoint inhibitors,” the authors said. “Here we demonstrate for the first time that a dynamic tumor microenvironment can distinguish differences between two different, anti-CTLA4 and anti-PD-1, against three different syngeneic mouse lines, MC38, ICI therapies CT26 and B16F10.”
Models recapitulating the tumor microenvironment have been in development for more than a decade. But they are typically static systems that do not capture the dynamics of lymphocyte migration and drug transport, and they are limited to a very short experimental duration due to the rapid decline in tissue viability, typically within 24 to 72 hours.
“An urgent need exists for engineered platforms capable of supporting viable tumor fragments for periods of a week or longer,” Borenstein said. “Our tests show that EVIDENT can accommodate dynamic interactions between lymphocytes and tumors and is compatible with real-time imaging and quantification of tumor killing and lymphocyte infiltration in response to ICI treatments.”
While it’s likely that animals will continue to play a key role in drug development, researchers are now trialing new treatments and, with platforms like EVIDENT, can opt to augment trials with tissue, including potentially human tumor tissue, that can be tested in real time.
“The main advantage to EVIDENT is speed and throughput, since we obtain an answer in seven days as compared to six weeks in a mouse, and we can run 12 experiments in EVIDENT versus one in a mouse,” Mott explained. “The other advantage is that we can observe mechanisms—minute-by-minute, if required—in an in vitro system that cannot be observed in a living animal.”
Julia Schueler, Research Director at Charles River Laboratories, said, “The EVIDENT platform is a valuable asset to oncology drug development because it has the potential to enable faster investigational new drug (IND) filings, as well as supporting animal welfare as an important contribution to the 3Rs principle (replace, reduce and refine).”
EVIDENT stands for Ex Vivo Immuno-oncology Dynamic ENvironment of Tumor biopsies. The system features organ-on-a-chip technology, flow-control using a single pump, low-absorption materials and the ability to connect to Draper’s customizable image analytic algorithms to provide automated and quantitative assessment of experimental results. EVIDENT enables cancer researchers to evaluate how ICIs and other drugs arm the immune system to kill tumors in a high-throughput, scalable configuration.
Charles River provided the materials used in the research.