Immune Checkpoint Specific Single Domain Antibody (SdAb) Development Solution

Application & Development Workflow Features Case Study Associated Services

The beneficial properties of single-domain antibodies (sdAbs) make them promising candidates for new immune checkpoint therapeutic applications. Creative Biolabs provides a complete package for developing sdAbs that target immune checkpoints for therapeutic and diagnostic applications. Tumors frequently manipulate immune checkpoints, which are essential regulatory pathways to escape immune detection, and these pathways become a main target in cancer treatment approaches. Creative Biolabs uses advanced platforms and technologies to deliver customized solutions that lead to the best possible results for clients.

Applications of Immune Checkpoint Specific SdAb

Checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 transformed cancer therapy while single-domain antibodies (sdAbs) gain recognition as valuable assets in this area. Small single-domain antibodies demonstrate exceptional potential as immune checkpoint inhibitors due to their compact size and superior binding affinity, along with their advantageous properties. Single-domain antibodies that target immune checkpoints demonstrate significant promise for molecular imaging because their high tissue penetration, combined with fast clearance, creates high-contrast images that improve patient selection and treatment tracking. These sdAbs develop a new platform for improving immune checkpoint-based therapies while driving forward molecular imaging and diagnostics.

An example of immune checkpoints. (Wierstra, et al., 2019)

With the profound knowledge of single-domain antibodies (sdAbs) for immune checkpoint targets and a mature sdAb platform, Creative Biolabs delivers tailored complete solutions for international customers. Creative Biolabs works directly with clients to create detailed proposals tailored precisely to their requirements, which support and improve scientific and clinical research involving immune checkpoint-specific sdAbs.

Typical Pathway for Immune Checkpoint Specific sdAb Development

Phase I Discovery

Target Identification
Target Identification Multiple target identification processes can be provided upon your request.
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Antigen Design and Preparation
Antigen Design & Preparation Starting with in silico sequence of targets, our scientists can handle the intact design and preparation processes to fit the demands for VHH discovery. You can also provide the prepared target for further processes.

Phase II SdAb Discovery

Immunization
Immunization Generation VHH from different host animals (e.g. llama, alpaca, camel, and shark) with various immunization strategies (e.g. DNA immunization, whole cell immunization, and multiple sites immunization) to meet your specific demands.
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Immune Library Based V<sub>H</sub>H Discovery
Immune Library Based VHH Discovery Our scientists are confident in generating high-quality immune library and performing comprehensive library screening and validation strategies to select the best-fit sdAbs for your targets.
Premade Library Based V<sub>H</sub>H Discovery
Premade Library Based VHH Discovery Creative Biolabs has owned a series of high-quality in-house VHH libraries (originated from camels, llamas as well as humans) which are great resources available for your VHH discovery project.
B-Cell Sorting Based V<sub>H</sub>H Discovery
B-Cell Sorting Based VHH Discovery To bring our customers impeccable service of VHH discovery, our seasoned scientific team has developed integrated B-cell sorting platform to maximize our customers' success in discovering valuable sdAbs.

Phase III Characterization

Functional V<sub>H</sub>H Screening
Functional VHH Screening A series of assays are available to further analysis and screening VHH candidates with desired functions, including but not limited to binding assays, immunomodulation assessments (activation or blocking), neutralizing assay, Fc profiling (ADCC, ADCP, CDC, etc.), endocytosis & internalization assays, cell proliferation assays.
V<sub>H</sub>H Affinity Measurement
VHH Affinity Measurement A series of technologies are available to measure the affinity of specific sdAbs with the most advanced systems (e.g. Biacore, ProteOn, Octet).
V<sub>H</sub>H Stability Evaluation
VHH Stability Evaluation A series of custom analytical approaches are available to assess the stability of specific sdAbs upon your request, including the evaluation of aggregation and stability under extreme condition.

Phase IV Development

Multivalent V<sub>H</sub>H Development
Multivalent VHH Development The development of multivalent VHH provides various alternative formats which can endow sdAbs with specific properties, such as extended half-life, increased avidity, and the recognition of different targets.
V<sub>H</sub>H Affinity Maturation
VHH Affinity Maturation Elaborate procedures can be tailored to develop sdAbs with increased affinity against the target of interest.
VHH Conjugation
VHH Conjugation A variety of custom VHH Conjugations are available of your choice.

Phase V Manufacture

V<sub>H</sub>H Scale-up Production
VHH Scale-up Production Transient transfection method can be employed for custom VHH production via either E. coli or mammalian system.
V<sub>H</sub>H Stable Cell Line Construction
VHH Stable Cell Line Construction Our scientists are professional in constructing stable cell lines with high yield to meet your demands of long-term VHH production.

Typical Features of One-Stop for Immune Checkpoint Specific SdAb Development

Creative Biolabs boasts unparalleled expertise in the discovery and development of single domain antibodies (sdAbs). Based on the most advanced platforms and powerful technologies, Creative Biolabs will offer custom solutions for the development of sdAb specifically binding to the immune checkpoint as a new diagnostic and therapeutic agent in cancer management. If you are interested in our service, please feel free to contact us for more details.

Reference

  1. Wierstra, Peter, et al. "Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer." EJNMMI Radiopharmacy and Chemistry 4 (2019): 1-20. Distributed under Open Access license CC BY 4.0, without modification.

Case Study

In this case study, we used one human target protein, one mouse target protein and one cynomolgus target protein for antibody library screening. The goal is to isolate cross-reactive sdAb binders that cross-bind to three genera of targets from our premade CaVHHL-S2™ camel synthetic single domain antibody library.

Fig.1 Library screening stage. (Creative Biolabs Original)Figure 1. Process monitoring of library screening stage.

This project used a solution screening strategy that alternated between human T1 and mouse T1. After four rounds of bio-panning, good enrichment of the target was observed, and a clear difference was observed between the control group and the control group.

Fig.2 Monoclonal phage ELISA and DNA sequencing. (Creative Biolabs Original)Figure 2. Summary of monoclonal phage ELISA of the randomly picked clones and DNA sequencing.

After library screening, clones were selected from the third and fourth rounds of output for monoclonal phage ELISA and DNA sequencing, and 10 unique clones were identified.

Associated Services

We are offering highly customized CRO services to assist your Single Domain Antibody (sdAb) related projects. Please Contact Us for more details.

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