The new wave of advanced immuno-oncology therapeutics including immune checkpoint therapies, targeted immuno-oncology treatments, and biomarker specific immunotherapies require that researchers have access to highly annotated, well-characterized primary human biospecimens.
While fresh human diseased samples have been used successfully, they suffer from several drawbacks that limit their utility, especially as demand grows for greater numbers of increasingly specific samples to drive research projects. The root problem with these fresh tumor samples is the time-sensitive nature of living tissue, but it manifests into an array of issues that arise to plague researchers. Live tissue samples from cancer resections for instance have a short period of time (days) in which they can be used, and it becomes difficult to schedule and complete everything that needs to be done in that window.
While fresh human diseased samples have been used successfully, they suffer from a number of drawbacks that limit their utility
Additionally, fresh samples tend to suffer from a lack of the proper characterization required for optimal sample selection. This can be as simple as not having time for a pathologist to confirm the diagnosis resulting in researchers receiving a different tumor indication from the one they were expecting. Fresh tissue samples typically can’t wait for biomarker testing prior to receipt and use, reducing the ability of researchers to properly characterize and select their samples. Researchers are often compelled to accept (and pay for) an entire tumor tissue which may be larger and more expensive than their needs justified. These are just some of the issues faced by researchers in working with fresh tissue samples, to say nothing of the transportation and logistical problems of transporting such sensitive material, making access to international samples almost impossible if not frighteningly expensive.
Cryopreserved, dissociated tissue cells (DTCs) overcome the time-constraint hurdles
The technology required for the dissociation and cryopreservation of solid tumors and normal tissue samples enables fresh tissue samples to be processed, preserved, characterized, stored, and shipped over much greater distances.
The advantage to this approach is that it eliminates the time constraint. Fresh tissue can be quickly transported to centrally located processing centers. On receipt these samples can be efficiently dissociated, processed into aliquots, and viably cryopreserved and safely stored in the vapor phase of liquid nitrogen. Furthermore, as the DTCs can be stored for long periods of time, a supplier can build up a repository of thousands of well-characterized disease state samples for researchers to choose from at leisure, assembling the ideal experimental population and performing additional pre-screening characterization prior to purchase.
These advances in the collection, processing, and storage are driving novel insights that help elucidate the complex tumor microenvironment at the single cell level without the need to source fresh tissue samples. Placing the tools required for the development of the next generation of therapeutics in the hands of researchers on a global scale.
The power of DTCs
Dissociated tissue cells represent the entire cellular composition of the parent solid tissue as viable, single-cell suspensions. DTCs are amenable to analysis by flow cytometry as well as a wide variety of other analytical tools to understand the complex cellular components of the tissue, as well as the surface expression of key therapeutically relevant proteins. A good example of this is the differential expression of PDL1 within different types of cancer. PDL1 is an important therapeutic biomarker as it is targeted by some of the most important immune checkpoint therapeutics including Keytruda® (Merck), Opdivo® (BMS), and Libtayo® (Regeneron Pharmaceuticals). Tumors with high levels of PDL1 expression are more amenable to treatment with these therapeutics, cancers that lack PDL1 are not. Having processed and characterized over 4,500 tumor samples into DTCs, Discovery has the experience and expertise to screen for biomarkers of interest and provide ideal sample cohorts to researchers seeking the insights required to develop the next tranche of advanced therapeutics.
Having processed and characterized over 4,500 tumor samples into DTCs, Discovery has the experience and expertise to screen for marks of interest and provide ideal sample cohorts
Maximizing the value of disease state samples.
Solid tumor specimens are precious. Unlike blood and bone marrow which can be drawn multiple times from the same donor, tissue samples such as solid tumors are typically only resected once. While core needle biopsies and fine-needle aspirates are more routinely performed, they provide only a limited quantity of material. By contrast, resection, where a solid tumor is surgically removed from a patient yields a significant quantity of primary, disease state tissue provided one can overcome the logistical demands of processing, annotating, cryopreserving, and storing, all within a brief enough time window to prevent any degradation of the sample.
Processing fresh tumor samples into DTCs allows us to capture and maximize the value from each of these precious, one-off samples, dissociating the tissue into its individual component cells, viably cryopreserving them, characterizing via flow cytometry, and storing the lot to be drawn upon for research at a future date.
Processing DTCs on a global scale.
Processing tissue samples into high-quality, viable DTCs is a non-trivial matter. Tissue samples are delicate, complex mixtures of cells and non-cellular material that must be teased apart and separated out to leave only live, viable cells without any background contamination. The quality of this processing is directly linked to the quality of the analytical data that can be derived from a DTC. In order to source sufficient samples to cover a broad spectrum of tumor types we need to cast a wide net, with clinical collection sites covering a broad, ideally densely populated geographic area. To facilitate this, Discovery Life Sciences has established a network of clinical collection centers across Europe and the US, served by two central processing centers where tissue samples can be processed in state-of-the-art facilities into DTCs. At the time of writing, Discovery has processed, analyzed, and cryopreserved over 4,500 unique tumor samples into DTCs. This extensive experience has allowed Discovery to refine best practice methods for the dissociation and analysis of tissue samples, processes which have been optimized for each different tumor and tissue type to ensure maximum recovery and viability, yielding the highest quality data during downstream analysis. In part two of this blog series, we will dig deeper into the best practices for DTC processing and analysis.
By profiling such a large volume of unique tumors Discovery has identified indication-specific trends in terms of tumor and immune content, trends that are specific to different cancers and that provide important insights for researchers working on the next generation of cancer therapeutics. In the third and final part of this blog series, we will discuss some of these patterns and their relevance to the treatment of disease and the development of new therapeutics.
By profiling such a large volume of unique tumors Discovery has identified indication-specific trends in terms of tumor and immune content, trends that are specific to different cancers and that provide important insights for researchers
This blog series is based on the Discovery DTCs User Guide, a comprehensive guide to best practices in DTCs, and details of the indication-specific patterns uncovered by Discovery as part of their work on disease tissue samples. You can download the full pdf at the link below.
References
1. Discovery DTCs User Guide, a comprehensive guide to best practice in DTCs. 2022. Discovery Life Sciences. [online] Available at https://www.dls.com/resource-hub/white-papers/dtcs-user-guide [Accessed 15 April 2022]
