Developing anti-cancer treatments is a top priority for biotech and pharma. In fact, an article in Future Science states, “Cancer remains the second leading cause of death after cardiovascular diseases, with 9.6 million victims worldwide… Cancer deaths are projected to increase by 60% in the next two decades.”
The need for effective immunotherapies worldwide is clear.
However, there are many challenges in developing immunotherapies that are effective on more than just a subset of patients. To better understand the challenges, analyze success stories, and learn how targeted RNA-sequencing can be incorporated into preclinical drug development, we spoke with Linda Xue, Ph.D., Principal Scientist and Bonnie Chen, Ph.D., Senior Director of the Next Generation Sequencing Department at Crown Bioscience.
In terms of developing anti-cancer treatments, there are challenges and limits. For example, only a subset of patients benefit from therapies that enhance anti-tumor immunity. With that in mind, what is playing an increasingly important role in improving immunotherapy?
Linda Xue and Bonnie Chen: There are multiple challenges in developing anti-cancer treatments. First, there’s the complexity of the immune system and the ability of tumors to evade immune system surveillance. Then, there are limitations in our current understanding of the mechanism of action (MoA) of immunotherapy. And finally, the responses to immunotherapy treatment remain limited to subgroups of patients.
Selecting multiple investigational strategies that aim to overcome the immunosuppressive functions can be used to enhance anti-tumor immunity. Checkpoint blockade can also be a rational strategy for effective anti-tumor responses and lead to successful immunotherapy drug development.
To apply these strategies efficiently, the evaluation of tumor immunity needs to be implemented across the wide range of preclinical immuno-oncology (I/O) models that are studied.
Crown Bioscience works closely with our clients to achieve time and cost-efficient preclinical studies to accelerate their drug development. One of the things that makes partnering with us unique: customers can utilize our complementary databases, which cover comprehensive profiling and historical data to choose the best models for their studies. We also provide multiomics biomarker analysis and bioinformatics support to maximize the value of the preclinical studies and accelerate our customer’s drug development.
Can you talk about what’s driving the shift towards next-generation RNA-Seq and how it’s enabling researchers to meet or fast-track project deadlines?
Linda Xue and Bonnie Chen: Traditional microarray technologies still lack accuracy and dynamic range. For example, probes are limited when it comes to sensitivity and specificity, and their ability to characterize mouse immune cell lines remains suboptimal. At the same time, protein-level biomarker assays, such as flow cytometry and immunohistochemistry, are also limited by the availability of ideal antibodies and lack of throughput.
As a result, researchers have a need for more efficient and robust analysis of preclinical I/O and tumor microenvironment (TME) study samples. We see this particularly in preclinical large-scale screening of immunotherapies, and this has prompted researchers to turn to RNA-Seq.
Next-generation RNA-Seq technology is a powerful, accurate, cost-effective, and rapid I/O analysis method that enables researchers to accelerate their drug development timelines because it overcomes many of the barriers of current technology. Additionally, the next-generation sequencing (NGS) technology has undergone significant cost reductions in recent years, making it a more approachable and cost-effective option compared to traditional sequencing technologies.
We use NGS technologies to quickly, accurately, and cost-effectively profile oncology models and experimental samples. This helps clients better understand cancer and tumor models, assist model selection and preclinical studies, uncover drug MoA, and accelerate drug development.
How is Crown Bioscience partnering with researchers and scientists to leverage next-generation sequencing (NGS) for preclinical drug development? Where have you seen this be most helpful?
Linda Xue and Bonnie Chen: By using NGS technologies, we can comprehensively profile preclinical models or any samples derived from preclinical studies. This data is very helpful in studying tumor development, understanding intra and inter-tumor heterogeneity and the TME and investigation of drug MoA. NGS technologies can also be helpful with the discovery of diagnostic and predictive biomarkers that can be applied in the following preclinical or clinical phases.
We have successfully helped our clients with their preclinical research by leveraging NGS technologies for dozens of projects and thousands of samples every year. We can also use NGS data with in vivo and/or in vitro studies for biomarker discovery.
Genomic/transcriptomic profiling of oncology models and experimental samples by NGS technologies is one of the most powerful ways to understand cancer and study drug MoA. Introducing biomarker strategies early in preclinical studies may accelerate the discovery and validation of predictive biomarkers, with the goal of de-risking drug development to increase the likelihood of clinical success for therapeutic candidates.
In your recent whitepaper, you describe how mouse immuno-oncology targeted RNA-Seq panels are available to evaluate genes that are associated with tumor immunity. Can you talk more about this and how you partner with pharma and biotechs on large-scale projects?
Linda Xue and Bonnie Chen: To accelerate immuno-oncology studies and immunotherapy development, we developed an NGS-based mouse I/O panel. This panel measures expression of 1,080 genes covering immune cell signatures, surface markers, transcriptomic immune cell-specific biomarkers, and key pathways at the interface of the tumor, TME, and immune response.
We also include signature and functional genes for many immune cell lineages, accounting for differences between different mouse strains. Targeted RNA-Seq on I/O related genes and pathways is also advanced in detection sensitivity and precision, with over 10 times sequencing coverage compared to conventional RNA-Seq in target molecules/pathways.
Our overall turnaround time from receiving a sample to reporting is only three weeks. Mouse IO RNA-Seq panel analysis is easily streamlined with preclinical studies, including our large-scale in vivo screening platform, MuScreen™. You can quickly and efficiently test a wide range of syngeneic and tumor homografts, covering various tumor types and indications with our platform.
Additionally, tumor or other tissue samples from each experimental group are collected for Mouse IO RNA-Seq panel analysis. This helps us clearly identify different expression patterns and immuno-oncology features/profiles for different pharmacological conditions and share this information with our customers so this can inform their immunotherapy drug development.
Want to learn more about the ways you can partner with Crown Bioscience and how you can leverage targeted RNA-Sequencing for your preclinical drug development? Read their whitepaper here and contact Crown Bioscience on the Science Exchange Marketplace.
Crown Bioscience, a JSR Life Sciences company, is a global contract research organization (CRO) providing discovery, preclinical and translational platforms to advance oncology, immuno-oncology, and immune-mediated inflammatory diseases.