2022 Virtual 3D Cell Culture Summit | Key Takeaways | Corning

The 2022 Virtual 3D Cell Culture Summit held this June brought together industry leaders and innovators to capture the explosion in 3D cell culture and its impact on the drug development process. The summit saw experts share ideas and explore the future of 3D applications, including spheroids, organoids, and tissue models.

Delegates discussed the value of patient-derived organoids in the drug discovery and clinical monitoring pathway. In addition to best practices, they also learned practical approaches, such as the Corning® Matribot® bioprinter, for workflow optimization creating scalable screening arrays.

The potential impact is huge. Currently, drug development companies invest around 10 to 15 years at 1 to 2 billion dollars, but with around 90 percent of clinical drug discovery failing. However, 3D cell culture shows promise for personalized medicine solutions to optimize clinical treatment and facilitate scalability for faster, more efficient drug discovery and screening.

Here are more key takeaways from the Virtual 3D Cell Culture Summit.

Patient-Derived Organoids: A Platform to Improve Drug Discovery and Development

Sylvia Boj Ph.D., chief scientific officer for HUB Organoids, described how patient-derived organoids (PDOs) were creating living biobanks of clinically relevant tissues for drug screening and clinical monitoring. To illustrate this, she presented key case studies on how these applications are impacting drug discovery and development in a variety of disease indications.

Boj provided evidence from studies on PDOs in colorectal cancers, showing they retained cell markers and phenotypes from the primary tumor. Studies also confirmed that the production process did not favor one mutation over another, meaning that the full spectrum of colorectal cancers could be studied.

In terms of the drug development process, the capacity for scalability and reproducibility has easily accelerated steps in drug discovery. Boj suggests that 3D cell culture with PDOs is valuable in hit generation and lead optimization, speeding up the process from exploratory research to candidate drug selection. She described how the first organoid-based drug is in the clinical phase of testing, having been through high content screening in tumor and human tissue 3D cultures. The pathway took only five years, from initial screening of 5,000 potentials through 52 hits, leading to clinical trial phase I for optimizing one bispecific antibody.

Boj also described how PDOs impact clinical management. Pretreatment PDOs show clinical predictive value for personalized preclinical testing and drug selection, and mimic patient clinical responses to therapy. This is valuable in oncology and cystic fibrosis, where individual patient tissue mutations determine response to treatment.

Key Takeaways: PDOs are very similar to the tissue they're derived from, retaining tumor heterogeneity and typical variation in drug response. They are genetically and phenotypically stable in culture and cryopreservation, so scaling up for a full drug discovery platform is feasible and extremely efficient.

3D Cell Culture as a Model of Small Cell Lung Cancer Brain Metastasis

Amanda Linkous Ph.D., scientific center manager for the NCI Center for Cancer Systems at Vanderbilt, spoke about the value of 3D cell culture for research into the biology of small cell lung cancer (SCLC). More than half of SCLC patients develop brain metastases, with a lower than five percent, five-year survival rate. SCLC is extremely aggressive and heterogeneous, and seen in around 15 percent of all lung cancers.

Studying SCLC metastasis has previously required in vivo mouse models, and while they're living, they don't provide the same "human" microenvironment for tumor invasion. Moreover, tumor implantation usually takes around three to six months to progress.

Human cerebral organoids support a number of SCLC tumor cell lines, both neuroendocrine and non-neuroendocrine. These mini brains mimic the in vivo microenvironment, showing choroid plexus development and cortical layering. They also allow SCLC tumor cell proliferation and maintain tumor heterogeneity and phenotype as found in patients. The mini brains support invasion and growth, so they're ideal for studying not only oncogenesis, but also the response to chemotherapeutic drugs.

These are also easily scalable, so researchers can create hundreds of them from stem cells for screening large numbers of drug combinations, concentrations, and time points. High throughput screening and imaging studies show tumor cell volumes within each 3D cell culture for characterizing the response.

Key Takeaways: Mini brains provide a 'normal' human microenvironment in which to study SCLC tumor growth and invasion. These cerebral 3D cultures support a shortened tumor latency with distinct invasion patterns maintained, which offers a faster in vitro alternative to in vivo mouse brain implantation testing.

Corning® Matribot® Bioprinter Printed Domes for Organoid Drug Testing

Hilary Sherman, senior scientist at Corning Life Sciences who works extensively with 3D cell culture applications, demonstrated how the Corning Matribot bioprinter could streamline the workflow for consistency and reproducibility.

Using a pancreatic cancer PDO assay as an example, Sherman explained how bioprinting could be a valuable in vitro tool in the drug development process. Best practices for creating a PDO assay with the Matribot bioprinter included key features of the instrument, such as programmable software and full automation.

Emphasizing accuracy for droplet and dome dispensing, Sherman showed how the bioprinter dispensed uniformly across a 96-well plate, leading to low variation between wells with a coefficient of variation below 15 percent. High throughput imaging could then easily assess 3D culture response to chemotherapeutics for highly reproducible results that could screen multiple drugs for the best choice in personalized therapeutics.

Key Takeaways: The Matribot bioprinter handles a wide variety of biological tissue and cell culture materials. The ability to program delivery means that bioprinting is highly reproducible across many tissue culture vessels. Uniform dispensing with low variability from well to well means that PDO assay data is both valid and sensitive to drug-dependent responses.