Ex vivo culture of human biopsies with idenTx: leveraging the STING pathway to complement NK-cell therapy

In a recent publication in Cancer Immunology Research, a team led by scientists at Dana-Farber Cancer Institute and Brigham and Women’s Hospital used AIM Biotech’s idenTx drug discovery platform to demonstrate the therapeutic potential of STING (stimulator of interferon genes) agonists in combination with NK cell-based therapies. In doing so, the team makes extensive use of ex vivo culture of human biopsies as an essential modality for evaluation of potential immunotherapeutic approaches.
Many lines of cancer research pursue the goal of harnessing the innate antitumor activity of the human immune system to both fight cancer directly and to facilitate introduced immunotherapies in doing the same. While activation of the STING pathway has been implicated in antitumor immune response, STING agonists have not yet been successfully developed as a clinical therapeutic. This is in part due to a range of deleterious effects on T cells concurrent with the desired antitumor activity. However, recent studies in mouse models have raised interest in the ability of STING agonists to interact with other targets in the tumor microenvironment (TME), including NK cells.

In order to more directly understand the interaction of STING agonism with the unique aspects of the human TME, the researchers leveraged assays based on human patient-derived organotypic tumor spheroids and human mesothelioma cancer cell spheroids within the environment of AIM Biotech’s idenTx microfluidic drug discovery platform.

In a pivotal series of experiments, idenTx was loaded with human tumor tissue in the central gel chamber while experimental treatments including STING agonists and NK cells were loaded into one of the side media channels. In this way, interactions between drug treatment, immunotherapeutic cells, tumor cells and the resulting TME were directly interrogated through quantitative imaging.

Key findings indicated that while cytotoxic to T cells and therefore potentially limiting to TCR T or CAR T therapies, STING agonists induced no cytotoxic effects on NK cells. In fact, STING agonists enhanced antitumor responses of both primary NK cells and engineered CAR NK cells.

The ability to recreate the human TME is critical to the evaluation and development of novel therapeutic compounds, mechanistic pathways, immunotherapies and combination therapies. Here, doing so through utilization of AIM Biotech’s idenTx 3D culture models in conjunction with human patient-derived tumor tissue advances development of novel therapeutic modalities leveraging STING agonists, but also provides a modality to more broadly interrogate therapeutic interactions through detailed recapitulation of the human TME.

This publication is the latest of over 140 peer-reviewed studies leveraging AIM’s idenTx organ-on-a-chip technology to break new ground in research and drug discovery in fields from immuno-oncology to neurobiology. You can see this study and more here.

Gathering more predictive, human-relevant data is what AIM Biotech is all about. Want to discuss how idenTx can transform your drug discovery research? Use the chat bubble on the bottom right corner of this page, and we’ll reach out to you—or check out our Contact Us page. Also be sure to look at how our own contract research servicescan help streamline your workflow.