Government investment in tissue chips
Efforts to commercialize organs-on-chip platforms and translate them for nonengineers have also picked in recent years. Several companies in the United States (including Emulate, a Wyss start-up) and in Europe now offer microengineered lung tissue models that can be used for research and drug testing. And some large pharmaceutical companies, said Dr. Tagle, have begun integrating tissue chip technology into their drug development programs.
The FDA, meanwhile, “has come to embrace the technology and see its promise,” Dr. Tagle said. An FDA pilot program announced in 2021 – called ISTAND (Innovative Science and Technology Approaches for New Drugs) – allows for tissue chip data to be submitted, as standalone data, for some drug applications.
The first 5 years of the government’s Tissue Chip for Drug Screening Program focused on safety and toxicity, and it “was successful in that model organ systems were able to capture the human response that [had been missed in] animal models,” he said.
For example, when a liver-tissue model was used to test several compounds that had passed animal testing for toxicity/safety but then failed in human clinical trials – killing some of the participants – the model showed a 100% sensitivity and a 87% specificity in predicting the human response, said Dr. Tagle, who recently coauthored a review on the future of organs-on-chips (Nature Reviews I Drug Discovery. 2021;20:345-61).
The second 5 years of the program, currently winding down, have focused on efficacy – the ability of organs-on-chip models to recreate the pathophysiology of chronic obstructive pulmonary disease, influenza, and other diseases, so that potential drugs can be assessed. In 2020, with extra support from the Coronavirus Aid, Relief, and Economic Security Act, NCATS funded academic labs to use organs-on-chip technology to evaluate SARS-CoV-2 and potential therapeutics.
Dr. Ingbar was one of the grantees. His team screened a number of FDA-approved drugs for potential repurposing using a bronchial-airway-on-a-chip and compared results with 2D model systems (Nat Biomed Eng. 2021;5:815-29). Amodiaquine inhibited infection in the 3D model and is now in phase 2 COVID trials. Several other drugs showed effectiveness in a 2D model but not in the chip.
Now, in a next phase of study at NCATS, coined Clinical Trials on a Chip, the center has awarded $35.5 million for investigators to test candidate therapies, often in parallel to ongoing clinical trials. The hope is that organs-on-chips can improve clinical trial design, from enrollment criteria and patient stratification to endpoints and the use of biomarkers. And in his lab, Dr. Huh is now engineering a shift to “organoids-on-a-chip” that combines the best features of each approach. “The idea,” he said, “is to grow organoids, and maintain the organoids in the microengineered systems where we can control their environment better ... and apply cues to allow them to develop into even more realistic tissues.”
Drs. Antony, Linkous, and Tagle reported no relevant disclosures. Dr. Huh is a co-founder of Vivodyne Inc, and owns shares in Vivodyne Inc. and Emulate Inc.