Introduction to pH-Sensitive VHH Discovery by Phage Display

The VHH antibodies (VH derived from heavy chain antibodies), also known as single domain antibody (sdAb), comprises only one heavy chain variable region and CH2, CH3 region. Unlike other antibodies, it lacks a light chain naturally. VHH is the smallest naturally occurring fragment capable of binding to antigens. Its small size, stable performance, and precise antigen specificity render it advantageous. These qualities make VHH applicable in diverse fields, including pharmaceuticals and biological research, such as disease diagnosis and treatment. Furthermore, the development of pH-sensitive VHH is of significant value, especially in the weakly acidic tumor microenvironment. pH-sensitive VHH enables targeted tumor therapy. Leveraging our extensive expertise and phage display platform, Creative Biolabs offers comprehensive services to facilitate pH-sensitive VHH development.

Antibodies. (Creative Biolabs Authorized)

pH-Sensitive VHH

Antigen-specific VHHs are selected by panning phage libraries over immobilized antigens, such as those encapsulated on test tube surfaces, biotinylated antigens attached to streptavidin beads, or membrane proteins expressed on cell surfaces. Some labs construct semi-synthetic libraries using cassette mutagenesis of CDR regions. The latter method allows the selection of antibodies against toxic or challenging-to-express antigens. However, VHH derived from non-immunized libraries usually exhibit lower affinity for their antigens compared to those obtained from multiple immunizations.

Recombinantly expressed VHH offers several advantages over conventional antibodies and scFv derived from the V structural domain of conventional antibodies. Their high thermal stability, multiplexing ability, and excellent in vivo tissue permeability make sdAbs suitable for various biotechnological and therapeutic applications. Moreover, VHH can be easily cloned into various forms by fusing with other proteins or peptides, allowing customization for specific diagnostic and/or therapeutic applications.

VHH demonstrates a wide array of applications in cancer therapy, owing to its high affinity and specificity. Its single domain structure facilitates precise targeting of receptors on cancer cells, particularly in areas with limited blood vessels. Additionally, VHH's low immunogenicity allows for repeated administration without triggering humoral or cellular immune responses, a crucial aspect in disease treatment. Moreover, pH-sensitive VHH exhibits enhanced tumor targeting properties by modifying its structure. Through the addition of pH-sensitive amino acid residues and side chain motifs, VHH can be rendered pH-sensitive active. Studies have highlighted the superior tumor targeting and specificity of pH-sensitive biomolecules, making them ideal for targeted drug delivery and therapy at tumor sites.

In the realm of in vitro diagnostics, VHH plays a pivotal role due to its robust epitope recognition and binding capabilities. Remarkably, its construction and expression processes do not necessitate purified antigens. The compact size of sdAbs allows them to firmly bind to solid-phase carriers, capturing trace antigens effectively. Consequently, VHH-based immunoassays prove invaluable in detecting challenging clinical targets, foreign pathogens, and toxins. For instance, the overexpression of EGFR in various tumors make it an attractive drug target. VHH targeting EGFR has been successfully utilized in diagnosing of breast, ovarian, and prostate cancers. Additionally, sdAbs find applications in molecular imaging techniques like positron emission tomography, single-photon emission computed tomography, near-infrared fluorescence imaging, and ultrasound molecular imaging for disease diagnosis.

At Creative Biolabs, we possess extensive knowledge and experience in the realm of pH-sensitive monoclonal antibodies. We are enthusiastic about sharing our expertise in pH-sensitive VHH discovery.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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