Tungsten VHH Phage Display Library
Our Tungsten VHH library for nanobody discovery contains two computationally designed libraries.
- An optimal camelid framework for reagent and diagnostic development
- An optimal human VH3-23 engineered VHH antibody framework for therapeutic development
The humanized VHH antibody library is comprised of more than 500 million clones, and the camelid library is even larger with a diversity of 2.6e9 unique clones. We have run more than 80 successful antibody discovery campaigns, with 25% of those leveraging the Tungsten VHH library.
Phage Display Offers Speed and Selected Specificity
Our libraries can deliver 100+ target specific nanobodies and this technology is the fastest approach. In contrast to immunization approaches, VHH phage display enables selections to be optimized towards rare epitopes, species cross-reactivity, and highly tuned specificity.
Additionally, phage display offers shortened lead discovery time because the llama immunization step is removed. This allows for a rapid development and potentially to be the first in class.
We can optimize your lead to introduce murine and cyno cross-reactivity, as well as identify new leads that are species cross-reactive. Meet our Antibody Discovery team.
The Tungsten VHH library for nanobody discovery successfully achieves target selectivity. We are able to stringently select for binders that distinguish between closely related protein family members. This is critical especially in the scenario where control over unwanted immune cell activation is needed.
Thermostability and Biophysically Stable Nanobodies
Therapeutic antibodies must exhibit favorable pharmaceutical properties, including high thermostability and low aggregation propensity in order to facilitate manufacturing and storage, as well as to promote long serum half-life.
We applied our thermal tempering technology to further optimize the thermostability and expression quality of our Tungsten VHH antibody library for nanobody discovery clones. Stability has positive impact downstream on therapeutic antibody developability.
Our Single Domain Antibody Library is Optimal for CAR-T Applications
Several factors in the CAR design have been identified as influencing the safety and efficacy of CAR-T therapies. In particular, the selection of the tumor-targeting moiety, with its exquisite specificity and desirable biophysical attributes, along with appropriate affinity. These factors coupled with robust downstream workflows to identify off-target binding, are all significant in developing a successful CAR or cell therapy.
In the above diagram, the CAR construct generally consists of four major domains: 1) the antigen binding domain, 2) the hinge region, 3) the transmembrane domain, and 4) the intracellular signaling domain.
In cell therapy, altered patient T-cells expressing a chimeric antigen receptor, including a scFv or nanobody fragment, on their surface is used to treat certain blood cancers. A sample of a patient's T cells are collected from the blood, then modified to express chimeric antigen receptors (CARs). When these CAR T-cells are reinfused into the patient, the new receptors enable them to latch onto a specific antigen on the patient's tumor cells and kill them.
Clients have reported <5% tonic signaling amongst the binders delivered using this VHH library for nanobody discovery. Studies showed that improvements in CAR stability translated to improved CAR surface expression, enhanced in vitro cytotoxicity, unwanted toxicities, and reduction in tonic signaling.
The Tungsten VHH library for nanobody discovery is robust, enabling the delivery of large panels of unique binders with a range of affinities which can then all be assessed to determine the appropriate affinity and specificity required for successful translation.
Once binders have been identified using our Tungsten VHH library for nanobody discovery, they can be engineered into the whole CAR construct, and then taken to our additional work streams. This enables a full, frictionless, and start-to-finish solution for CAR programs.
Frequently Asked Questions (FAQs) About Tungsten VHH Library for Nanobody Discovery
What’s the typical workflow using your VHH library for nanobody discovery?
We start panning on soluble protein after all reagents have passed an initial QC of the reagents. We pick 1104 single bacterial colonies that each express a unique nanobody, and that have been enriched for binding to the antigen. Sanger sequencing of hits and screen occurs via high throughput cell binding assay by FACS and for kinetics.
Output includes all nanobody sequences that bind in cell-binding assay and bind in the kinetic assay with the on/off rates and affinities.
Optionally, we can reformat the selected best 48 nanobodies and reformatted to VHH-Fc. These molecules are then expressed, purified, and confirmed for binding as VHH-Fcs either in cell-based format or kinetically.
Can I use the same exact molecule for preclinical studies?
There is no need to create a surrogate antibody when advancing to the clinic. Since we can discover mouse/cyno/human cross-reactive lead candidates, there is no need to create a surrogate antibody. This allows you to avoid risks that can sometimes appear in your translational studies when using the Tungsten VHH library for nanobody discovery.
How can I speed up antibody discovery and development to ensure I am first to market?
It’s possible to obtain target-specific single chains or nanobodies using the VHH antibody library for nanobody discovery in as little as two months. We have a comprehensive antibody discovery and development platform, including the SuperHuman antibody library, offering the diversity to deliver therapeutic leads against the hardest targets. This includes GPCRs, ion channels, pMHC complexes, anti-HIV bnAbs, allosteric modulators, mouse/human cross-reactive epitopes, anti-idiotypics, and bi-epitopics. By utilizing our end-to-end services, you can reduce time and cost for your biologic project. We proudly offer:
Is there a need to do llama immunization when using the Charles River Tungsten VHH antibody library?
Our Tungsten libraries are optimized nanobody libraries. They are ready to be used and no separate llama immunization step is required when using our VHH library for nanobody discovery.
Is a VHH library for nanobody discovery suitable for bispecifics, CAR-T, reagents, and diagnostics?
Yes, biophysically stable nanobodies provide a flexible starting point for many downstream applications and multiple final formatting options.