Traditionally, immunohistochemistry (IHC) has been used primarily in diagnostic pathology to detect one or two markers per slide, often to classify disease or confirm a diagnosis. While this application remains essential, the field of histology has dramatically expanded with the use of multiplex immunofluorescence (mIF) labeling. Multiplex immunofluorescence, paired with stripping reagents or other specialty techniques, allows for the detection of 10+ markers in a single tissue section. A deeper understanding of the interaction of drug treatments on cancer or diseases can be investigated. This article will focus on the use of mIF as a tool within the drug discovery/development pipeline.
Overview of the drug development pipeline
A typical drug development pipeline usually follows five stages:
1) Discovery and Development. Researchers identify promising molecular targets and develop candidate drugs that modulate those targets.
2) Preclinical Research. Drug safety, efficacy, and pharmacokinetics are evaluated in animals or ex vivo systems.
3) Clinical Research. Testing in human participants through trials to assess safety, dosage, and therapeutic effect.
4) FDA Review. Regulatory assessment of all preclinical and clinical data for approval.
5) FDA Post-Market Drug Safety Monitoring. Ongoing evaluation of long-term safety, efficacy, and rare adverse events in the general population.
mIF’s Role Across the Drug Development Pipeline
The use of histological tools, such as mIF, is not as prevalent in stage 1 of the drug discovery process, but it becomes more useful and relevant in stages 2 and 3. During preclinical research (stage 2), mIF can be used to assess drug distribution or mechanism of action within non-human models. It is complimentary to other standard endpoints such as ELISAs or viability tests. The advantage of mIF is that it uses a single tissue section to answer important questions: Is the drug reaching its intended target? Are there any off-target effects triggering inflammation or cell death in healthy areas?
As therapies progress into clinical trials (stage 3), mIF becomes a powerful tool. When applied to patient tissue samples retrieved through surgical resections or biopsies, it can be used for assessment by giving insight into how a drug performs in the spatial and structural context of human biology. Looking at treatment effects at a cellular level can build on preclinical findings and answer even more important translational questions. For example, a multiplex panel can be designed to label immune cell markers and cancer markers to analyze a tumor sample pre and post treatment. This mIF approach combined with analytics can provide profound insights into the drug discovery process.
Looking Ahead
The applications of mIF can go far beyond what is traditionally possible with chromogenic staining. Whether you are at the preclinical stage or into clinical studies, Visikol can help you develop a mIF study for your specific research needs, reach out to a member of out team to learn more. In upcoming blog posts, we will explore specific use cases of mIF in more detail as well as how we can work with you to design or implement panels.
Author:
Tammy Tran
Associate Scientist