In new drug development pipelines, there is an increasing trend to switch from “small” to “large” molecules (also known as biologics). While the FDA guidance was quite specific with their recommendations for small molecules ADME-Tox studies, there is not much currently published for these large molecules.
The Japanese PDMA guidelines 2019 issue refers to some specificity regarding their internalization and degradation pathway. They are also well known to be prone to trigger cytokine release. The so called “cytokine storm” is one of the major toxicity events to be feared.
To support R&D projects around Biologics development, I have illustrated in this post what tebu-bio can offer in terms of reagents and services, including tools to monitor cytokine release (blood derivatives and cytokine multiplex assays), and reagents to help decipher their mechanism of action and catabolism.
Biologics and cytokine release: blood derived reagents
Cytokine release assays are commonly used to explore the potential “capacity” of biologics to induce pro-inflammatory cytokines secretion. In these assays, biologics are incubated with either whole blood or PBMCs. tebu-bio can supply both reagents, from catalogue PBMCs (healthy or diseased donors) to the supply of whole blood (frozen or fresh with short term delivery time frame)
Multiplex cytokine quantitation assays
Although IFN alpha, beta and gamma have often been related to therapeutic RNA inflammatory effects, other cytokines are also commonly involved in the process (IL-1β, IL-6, TNFα…). tebu-bio offers IFN related ELISA from PBL IFN specialist. For simultaneous monitoring of multiple cytokines, tebu-bio multiplex assay platform (based near Paris) offers you the possibility to outsource your sample analysis with robust technologies to produce quality data. This post illustrates the options we offer.
Biologics Mechanism of Action: signalling pathway profiling
As these large molecules have been less extensively studied than their small molecules counterparts, it is often more difficult to predict what their mechanism of action will be. Knowing more about how they interact with cellular events is often requested by funding bodies as a condition to move forward into the project. tebu-bio laboratories phospho-array platform can analyse your samples for phosphorylation events and provide you some clues about potential pathways activated by your molecule of interest. Whether you do not have any pre-concieved ideas about the signalling events (with a broad profiling array based on >1300 antibodies covering over 30 pathways), or whether you already have a hunch (large selection of pathway focused arrays for NF-kB, T-cell receptor, Jak/Stat, MAPK, PI3K/Akt, RTK, Apoptosis…). We can also help with biostats analysis.
Purified lysosomes for catabolism studies
In general, biological products are eliminated through internalization and degradation in lysosomes of the target cells, after binding with specific receptors on the cell surface. Taking this into consideration, Xenotech has developed active purified lysosomes to specifically study the catabolism of therapeutic RNA, proteins, polymers… This post will tell you more about this offer.
If your interest is more targeted towards immuno-oncology, you may wish to have a look at this recent post written by my colleague Frédéric.