VHH antibodies as biotherapeutics
Camelid heavy-chain only antibodies were discovered in the early 1990’s. Often referred to as VHH antibodies, they are a well characterized alternative to therapeutic IgG’s.
Camelid heavy-chain only antibodies have no light chain. The VHHs or Nanobodies constitute the binding domain of heavy-chain only antibodies. Nanobody technology was patented in mid-1990’s with patents expiring in 2014. They are now widely used and developed for therapeutics, diagnostics, and laboratory reagents. Camelid VHH antibodies are typically obtained via the immunisation of camelids (e.g Llama) or by using in vitro libraries.
Why choose a synthetic antibody library, over immunising a Llama?
- Large size – Over 1 million fold larger than libraries generated from natural sources, increasing the opportunity to source multiple novel biological candidates with high specificity and affinity
- Diversity – Constructed de novo, using state-of-the-art synthetic biology approaches. No animal immunisation or use of natural human repertoires from B cells.
- Innovative – Immunologically naïve maximising the discovery of potential therapeutic antibodies against a greater range of target epitopes
Features and benefits of VHH single domain antibodies
| Feature | Benefit |
| Same high affinity and specificity as IgG | Low chance of off-target effects Predictable mode-of-action |
| Multi-specific | T-cell recruitment Target multiple pathways at once Higher cell-specificity Reduced acquired resistance (escape mutants) |
| Modular | Customisable half-life Fusion with other bioactives (eg, ADCs) |
| Validated in clinic | Regulator awareness Industry confidence |
| Small size | Tissue penetration (ADCs) Targeting of inaccessible epitopes (GPCRs, Ion Channels, Enzymes) |
| High sequence homology to human VH | High homology = lower immunogenicity |
| pH and temperature stability | Shelf-life Alternative delivery routes (eg, inhaled) |
| Simple production | Low cost of goods Ease of manufacturing and technology transfer |
VHH – Clinical landscape: Increasing clinical validation of platform in multiple settings
There are currently 12 VHH antibodies in pre-clinical to phase III validation worldwide (souce Ablynx*).
In summary, a synthetic antibody offers greater opportunity to find a developable therapeutic antibody candidate within a short timeframe. Contact us to start your antibody discovery partnership with Isogenica.
Further Information
Isogenica’s LlamdA®(single domain VHH) library is entirely synthetic, providing a key advantage that VHH are generated to specific epitopes which are difficult to target using conventional immunisation methods. Leveraging its CIS Display and Colibra™ technologies to accelerate the discovery and development process, therapeutic antibodies are delivered that meet the highest standards of quality and developability.
Isogenica has the in-house capability and expertise to efficiently undertake and manage all discovery & development activities from programme start to development. In collaboration with biopharmaceutical partners over the last decade, Isogenica has developed a deep pipeline including two clinical assets (currently in Phase I and II respectively) and numerous partnered discovery and pre-clinical stage programs.
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