Target Proteins for Antibody Drug Discovery

Comprehensive portfolio of target proteins designed for every stage of antibody drug discovery campaigns.

Overview

Since the approval of the first antibody drug OKT3 in 1986, antibody drugs have occupied an important position in the pharmaceutical market. Currently, antibody drugs mainly come in various types such as monoclonal antibodies, bispecific antibodies, and XDCs (such as antibody-drug conjugates, ADCs). With the continuous development and improvement of monoclonal antibody technology, antibody drugs have become highly diversified in terms of target types, drug forms, and therapeutic areas. KACTUS, with its proprietary protein research and development production platform SAMS™, has launched various types of high-quality recombinant proteins to fully meet customer needs for antibody development.

Target Proteins for Antibody Discovery

In the early stages of antibody drug development, it is often necessary to use antigen proteins for animal immunization to obtain antibodies. KACTUS offers a wide variety of target proteins, all of which have undergone strict biological activity tests, aiding customers in animal immunization. Example data:

Figure 1. Our recombinant human β-Klotho protein exhibits excellent binding ability with its antibody (left graph, ELISA) and ligand FGF21 (right graph, SPR).

For multiple transmembrane protein targets, such as the GPCR family and the Claudin family, the presence of several hydrophobic regions makes it difficult to be solubly expressed and maintain activity. KACTUS adopts special designs, such as using virus-like particle (VLP) proteins for display, allowing soluble expression while maintaining the correct conformation and biological activity of the protein. Additionally, for proteins with poor direct immunization effects or weak immunogenicity, utilizing VLP display not only retains good biological activity but also achieves stronger immunization effects.

Figure 2. GPRC5D and GPC3, displayed using VLP, both exhibit good binding activity with their respective antibodies.

Figure 3. CD24, displayed using VLP, not only binds well with the antibody (left), but also shows a significant enhancement in immunization effects (right).

Biotinylated Target Proteins for Antibody Screening

After obtaining antibodies, it is necessary to screen and optimize the acquired antibodies. Proteins labeled with biotin have higher sensitivity and specificity, which can be used not only for various detection analyses but also for immune capture. They have unique advantages in analyses like ELISA, SPR, flow cytometry, and biopanning.

KACTUS offers both site-specific and non-site-specific biotinylated proteins for customers to conduct antibody screening tests. Site-specific biotinylated proteins utilize the principle that the lysine residue on the Avi tag can be modified with biotin by the biotin ligase BirA, enabling precise control of biotin modification. Moreover, when the protein is fixed to the surface of the affinity-coated bead, it has directional consistency and is widely used in various detection analyses.

Figure 4. Verified by ELISA, site-specific biotin-modified Human APRIL (Trimer) (left) and GDF15 (right) both exhibit good binding activity with their respective ligands.

Non-site-specific biotinylated recombinant proteins are produced by chemical labeling, where the free amino groups or lysine residues of the protein can bind with biotin. This method may have higher sensitivity as multiple biotins can be labeled on each protein molecule.

Figure 5. Verified by ELISA, non-site-specific biotinylated labeled HLA-G or HLA-E tetramers can be applied in blocking analysis experiments related to corresponding antibodies.

In addition, during the performance evaluation stage of antibody drugs, besides analyzing the binding situation between the antibody Fab fragment and the target, it is also necessary to analyze the binding ability of the Fc segment with the Fc receptor, to evaluate the antibody's half-life or the antibody’s ADCC effect. The Fc receptor protein series from KACTUS, including FcRn and various mutated forms of Fcγ receptors, can aid in antibody optimization and in obtaining antibodies with the desired affinity.

Figure 6. (Left) Verified by SPR, Trastuzumab can bind with Human Fc gamma RI, with an affinity constant of 1.94 nM. (Right) Verified by SPR, Human IgG1 can bind with Human FcRn, with an affinity constant of 0.28 µM.

Target Proteins for CMC Method Development

CMC (Chemistry, Manufacturing, and Controls) is one of the key links for the successful development and registration of a drug, requiring high-quality proteins with high stability to establish production control parameters and imposing higher requirements on the stability and activity of the proteins. KACTUS' recombinant protein products possess high stability and excellent activity, which can be applied in the CMC method development of antibody drugs. Example data:

Figure 7. Verified by ELISA, recombinant Human Trop-2 (left) and Siglec-10 (right) proteins exhibit good batch-to-batch stability.

Figure 8. Verified by SPR, both biotinylated Claudin 6-VLP (left) and biotinylated CD20-VLP (right) proteins can bind well with their respective antibodies.

Custom Target Protein Production

To cater to diverse and specialized requirements, KACTUS offers custom target protein production. We are committed to delivering a spectrum of target proteins and associated analytical services like SPR analysis, aligning with the intricate needs of antibody drug development endeavors of our clients.

Our refined and structured approach to developing customized target proteins includes:

Confidentiality Agreement

Technical Discussion & Protein Design

Expression Testing

Activity Testing

Antibody therapy has emerged as one of the most rapidly advancing treatment modalities, with innovative antibody discovery technologies fast-tracking the progression of antibody drugs into clinical stages. As an increasing number of antibody drugs receive approval, there is renewed hope for cancer patients for extended life expectancy and enhanced quality of life. KACTUS remains steadfast in its commitment to providing premium recombinant protein products, serving as a pillar of support for antibody drug research, with the ultimate goal of facilitating swift benefits to patients.