RNAscope assay: Single cell transcriptomics for drug target discovery
When dealing with biomarkers in drug target discovery, profiling the tissue transcriptome in its spatial organization is key to understanding and predicting that tissue’s response to immunotherapy, because the tissue function within the body relies on the precise spatial organization of the cells. This is especially true when dealing with complex and heterogeneous tissues, such as tumors.
With tumors, the relationship between the cells and their environment is what ultimately shapes a patient’s fate. Applying the RNAscopeTM assay allows that evaluation of the presence of transcripts within a spatial context. This technique then ultimately can predict the tumor’s response to immunotherapy.
To further explain the impact of the RNAscope assay, this application note details a case study on a non-small-cell lung cancer (NSCLC) sample to predict its response to immunotherapy. This case study:
- Investigates the presence of the PD-L1 drug target transcript and the Granzyme B (GZMB) biomarker of clinical outcome transcript
- Explains quality control measures taken to validate the hybridization technique
Looks at the heterogenous distribution of transcripts in the NSCLC tissue section & examines the quantification of the PD-L` and GZMB to draw conclusions on the tissue’s reaction
Personalized therapy selection: Investigation of multiple immune-checkpoints
PD1 blockade has changed the immunotherapy approach against solid tumors – prescribing patients’ monoclonal antibody-based therapy yielded positive results. However, the number of patients that benefited was small compared to expectations, and lack of attention paid to immunohistochemistry could be responsible. Understanding the tumor microenvironment with a single biomarker is not accurate enough to predict the interaction of the drug with the site of action, or to predict the effectiveness of the drug for the patient.
In this application note, industry expert, Corinne Ramos, PhD, discusses how understanding the tumor microenvironment (TME) at the biomarker level is not enough to predict the interaction of the drug with the site of action. Her study performs a deep spatial profiling of biomarkers on two baseline non-small cell lung cancer (NSCLC) tissue samples. The population of gene expression was characterized with a focus on a specific region of interest on the tissue where she could draw conclusions on the TME.
Her research walks through:
- Immune infiltration
- How phenotype correlates with ICI response
- T-cell-inflamed gene-expression profiles
- Immune suppressive pathways that reduce ICI activity
- Tight immune checkpoint targeting.
Learn why the TME needs to be investigated at the molecular level to accurately prescribe the appropriate therapy.
Top 8 Benefits of Mass Spectrometry Imaging Early in Drug Development
Mass spectrometry imaging (MSI) is a groundbreaking technology that provides visuals of complex biological samples to study a drug’s distribution and understand its potential toxicity. MSI can unlock crucial data and give scientists additional insights into drug discovery, diseases, and personalized medicine.
MSI is beneficial in early development and murine models across many therapeutic areas and is especially suited to oncology due to the availability of tissue. With MSI you can:
- Speed up and optimize the drug discovery process
- Visualize drug distribution in tissues and tissue sub-compartments
- Analyze samples for thousands of compounds at once
- Eliminate sensitivity and chemical alteration concerns
- Know whether efficacy is possible based on distribution
- Locate and identify metabolites to understand potential toxicity
- Improve understanding of pharmacokinetics and pharmacodynamics
- Save money and provide a competitive development edge
Download our infographic to learn more about the benefits of mass spectrometry imaging in oncology.
Validating the efficacy of a compound with spatial imaging
With the ever-changing drug development landscape, pharma and biotech companies have the challenging task to quickly and efficiently generate quality and unique data to file an IND. Spatial bioanalysis is a unique solution that can help you achieve this goal, while also enabling strategic and optimized decision making throughout your process.
Download this spatial bioanalysis white paper to gain insights from industry expert, Corinne Ramos, PhD. Discussion points include:
- Precision medicine development and added value
- Disease heterogeneity: Why is it? Why is it important? How do we visualize it?
Target discovery and development of composite biomarkers