One-Stop Solution for Anti-Membrane Protein VHH Antibody Development

Background Development Service Development Process Features Case Study Published Data FAQ Resources

Creative Biolabs is a leading service provider focusing on single domain antibody (sdAb) discovery and development. SdAb is an artificially designed antibody molecule, also known as VHH antibody or camelid antibody. Based on our deep understanding of various membrane proteins, our scientists have built up one-stop solutions to generate high-quality single domain antibodies that can properly recognize the target membrane protein for our customers all over the world.

Membrane Protein: A Class of the Most Important & Challenging Targets for Antibody Development

In most cancer diseases, therapeutic targets are cell surface molecules that are predominantly comprised of membrane proteins. Membrane protein is a class of targets that are composed of a wide range of structurally and functionally diverse proteins involved in a variety of important physiological and homeostatic processes, such as:

In terms of the ability to activate/block the downstream function or promote the analysis of 3D structure, antibodies that can direct against target membrane proteins have played critical roles as either therapeutic/diagnostic agents or research tools. However, membrane protein is also one of the most challenging targets to generate high-quality antibodies, and the limitations usually include:

1) The challenge of designing and producing properly antigens that can mimic the epitopes of naïve membrane proteins;

2) Homology issues that may cause immunological tolerance;

3) Potential steric issues caused by the multi-pass membrane proteins, in which some epitopes cannot be reached by conventional antibodies.

Developing High-Quality Anti-Membrane Protein VHH Antibody at Creative Biolabs

Fortunately, Creative Biolabs has solutions to overcome all these limitations by using VHH instead of full-length IgG or other antibody fragments. VHH is a unique antibody format that consists of a single monomeric variable domain without a CH domain or light chain in the conventional Fab region. It is usually generated from camelid or cartilaginous fishes, which indicate relatively low homology for most of the membrane proteins associated with therapeutic targets. Taking advantage of the small size, high stability, and great penetrability, VHH can carry out the task of recognizing even the most cryptic epitopes. In the meantime, our scientists have also integrated our Magic™ membrane protein platform and DNA immunization strategy into the profiles, which can offer comprehensive solutions for antigen design and preparation. Therefore, the development of single domain antibodies against membrane proteins is now highly sought after for research, diagnostic, and therapeutic purposes, and our one-stop solution could be the most efficient option to achieve your purpose with high success rates.

Typical Pathway for Membrane Protein-Specific VHH Development

Phase I Target Identification

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Phase II Discovery

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Phase III Characterization

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Phase IV Development

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Phase V Manufacture

Features of One-Stop Anti-Membrane Protein VHH Development

Creative Biolabs has developed a variety of VHH antibodies against membrane proteins with years of experience. We are always pleased to offer the best service and the most qualified outcomes to meet your specific requirements. If you are interested in developing novel VHH antibodies against the membrane protein of interest, please do not hesitate to contact us for more details.

Published Data

Fig. 1 SdAbs from Different Clones Demonstrate Specific Reactivity against MT1-MMP.1

Fig. 2 Biodistribution and Pharmacokinetics of [68Ga] Ga-NOTA-sdAbs.1

The article presents a comprehensive study on the development of anti-membrane type 1-matrix metalloproteinase (MT1-MMP) sdAbs for positron emission tomography (PET) imaging in triple-negative breast cancer (TNBC), underscoring the aggressive nature of TNBC and the significance of identifying biomarkers for improved patient outcomes. The article describes how a llama-derived sdAb library was generated and screened against the catalytic domain of MT1-MMP, resulting in the discovery of particular sdAbs. Following a comprehensive analysis, two of these sdAbs were tagged with gallium-68 (68Ga) and tested in a TNBC mouse model. The immunoPET imaging exhibited precise in vivo tumor targeting with high signal-to-background ratios, with (68Ga) Ga-NOTA-3CMP75 exhibiting more tumor uptake than (68Ga) Ga-NOTA-3TPA14. The imaging data was shown to be perfectly correlated with immunohistochemical staining results, demonstrating the sdAbs' selectivity for MT1-MMP. The results show that anti-membrane protein sdAbs have great specificity against MT1-MMP, making them intriguing candidates for PET imaging in TNBC and warranting further exploration as diagnostic tools.

Reference

  1. Mulero, Francisca, et al., "Development of anti-membrane type 1-matrix metalloproteinase single domain antibodies as immunoPET probes for triple negative breast cancer imaging." Frontiers in Medicine 9 (2022): 1058455. Distributed under Open Access License CC BY 4.0, without modification.

FAQ

1. What is the significance of targeting membrane proteins with VHH antibodies?
2. What are the benefits of targeting membrane proteins with VHH antibodies?
3. What are the advantages of VHH antibodies in recognizing conformational epitopes of membrane proteins?
4. What role do VHH antibodies play in the structural determination of membrane proteins?
5. How can VHH antibodies enhance the specificity of membrane protein detection and quantification?
6. What are the benefits of VHH antibodies in therapeutic and diagnostic applications involving membrane proteins?
7. In what ways can VHH antibodies be used to modulate the function of membrane proteins?
8. What is the impact of VHH antibodies on the advancement of membrane protein research techniques?
9. How do VHH antibodies contribute to the overall understanding of membrane protein biology?

Resources

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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