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Put Your Best Cells Forward: Overcoming the Challenges of Ion Channel Antibody Discovery

Blog Post_Ion Channel Antibody Discovery

With an estimated $12 billion in worldwide sales1, ion channel antibodies are the third best-selling group of prescribed drugs and a huge potential growth area. But the inefficiencies of traditional antibody discovery processes can oftentimes block the road to market approval in early-stage development.

Methods such as hybridoma and B cell sequencing comprise multiple manual time-consuming steps. Crucially, they can result in laboratories unknowingly disregarding promising candidates, which can stall development programs before they even get off the ground.

Such challenges are further compounded when working with ion channels which require antibodies with high specificity and selectivity. But an evolution in antibody discovery provides laboratories with the edge they need to accelerate and refine ion channel antibody development.

Challenges associated with traditional ion channel antibody discovery

For biologics, the long journey to market approval starts with the single step of antibody discovery, a process that has traditionally been tedious, arduous, and inefficient.

When using hybridoma, for example, a significant proportion of the original B cell repertoire dies at the fusion stage.2 Losing these candidates prevents researchers from learning about their characteristics or their potential to tackle unmet medical needs.

While B cell sequencing removes the fusion step, it is still far from ideal. Following isolation and sequencing, laboratories lack the analytical information needed to make informed decisions on which candidates to take forward. What’s more, post-reexpression functional analysis comprises multiple time-consuming assays.

These issues are further compounded when working with difficult targets, such as ion channels. Ion channels are a large family of polytopic membrane proteins that enable the passage of ions across cellular membranes. Present in all cell types, they modulate functions such as electrical excitability, secretion, cell migration, and gene transcription, meaning they are critical in a range of biological processes and disease mechanisms.1

It makes them an attractive therapeutic target, as demonstrated by the multitude of approved ion channel modulators, such as amlodipine, zolpidem, and alprazolam, that have been huge commercial successes.3 And with only a handful of the estimated 400 annotated ion channel genes in the human genome so far being targeted,1 the opportunity to develop more impactful ion channel therapeutics is clear. Unlocking that potential, however, is not without its challenges.

Ion channels are transmembrane proteins and have very small exposed areas of extracellular epitope, which inhibits binding during the discovery process.1 This drives the time to lead molecule selection up even further, and reduces the likelihood of achieving quality hits.

Set all this to the backdrop of the fast growing, fiercely competitive biologics market, and it is clear that organizations wanting a competitive edge will need a new approach.

Higher quantities of quality hits with the Beacon Platform

The Opto® B Cell Discovery Workflows, performed on Bruker Cellular Analysis’ Beacon® optofluidic system, represents an evolution in antibody discovery, even for difficult targets like ion channels.

By moving functional profiling to the beginning of the screening process, the Opto B Cell Discovery workflow can identify potent ion channel candidates in a single day and provides researchers with all the information they need to make informed lead molecule section decisions after sequencing and re-expression. Profiling assays can be adapted to difficult targets, such as ion channels, with the use of antigen expressing cells that increase binding properties.

The automated, function-first approach to B cell profiling enables the discovery of 10-fold more quality hits against difficult transmembrane targets, including ion channels, when compared to hybridoma4.

The Beacon system empowers researchers to always put their best cells forward – and to get ahead of the curve in the race to develop ion channel-targeting molecules.

If you are ready jumpstart your antibody discovery programs, get in touch with one of our experts.

  1. Wilkinson, T. C., Gardener, M. J., & Williams, W. A. (2015). Discovery of functional antibodies targeting ion channels. Journal of biomolecular screening20(4), 454-467.
  2. Pedrioli, A., & Oxenius, A. (2021). Single B cell technologies for monoclonal antibody discovery. Trends in immunology, 42(12), 1143-1158.
  3. Pharmacology Education Project. Ion channels. (n.d.) Available at: https://www.pharmacologyeducation.org/pharmacology/ion-channels Last accessed: 2 March 2023
  4.  Genovac on Antibody Discovery. Going Where Hybridoma Can’t Available at: Genovac on Antibody Discovery – Bruker Cellular Analysis Last accessed: 13 July 2023
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