Tungsten VHH Phage Display Library

Our Tungsten VHH library for nanobody discovery contains two computationally designed libraries.

  1. An optimal camelid framework for reagent and diagnostic development
  2. 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.

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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.

The CAR construct generally consists of four major domains: the antigen binding domain, the hinge region, the transmembrane domain, and the intracellular signaling domain.

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.

Watch this video series to learn how failures in late-preclinical and clinical stages can be avoided if the appropriate early CAR discovery activities are performed

Thinking With the End in Mind

Failures in late-preclinical and clinical stages can be avoided if the appropriate early CAR discovery activities are performed. Learn more about common pitfalls and how to avoid them.

Watch the series

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.

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Frequently Asked Questions (FAQs) About Tungsten VHH Library for Nanobody Discovery