Anti-Idiotypic Antibody Discovery Service for PK Assay

Overview of Our Services

Therapeutic antibodies are the fastest growing class of drugs in the treatment of cancer, inflammatory diseases, and autoimmune disorders. Sensitive pharmacokinetic (PK) assays and immunogenicity assessment are required in the development process for biotherapeutic proteins. Ligand binding assays (LBAs) are often used to determine the PK profile by quantitating the therapeutic protein in biological matrices such as serum. However, high specificity and binding activity are necessary for the application of LBAs. Therefore, anti-idiotypic antibodies targeting the idiotypic determinants of individual antibody drugs are recognized as perfect reagents for such LBAs. Based on our skilled groups and mature technologies, Creative Biolabs has launched a series of anti-idiotypic antibody products as well as customized one-stop services. After more than a decade's labor, we have established advanced immune antibody library construction and screening methods platforms to meet our customers' needs.

Introduction of Anti-idiotypic Antibody and PK Assay

Due to the total humanization of developed therapeutic antibodies, the drug becomes hidden within the high concentration of very similar antibodies in human serum, which brings difficulties to detect and quantify. In order to measure drug levels with a PK assay, anti-idiotypic antibodies with high specificity only bind to the antibody drugs but not to the vast excess of similar Ig molecules is necessary.

Fig.1 Antibody idiotope.¹

The structure in the variable regions of an Ig, specifically the complementarity determining regions (CDRs) that confer its antigenic specificity, is known as the idiotype. It is obvious that the idiotopes are unique for each antibody which determines the binding capacity of different anti-idiotypic antibodies.

Applications

Anti-idiotype antibodies represent a class of reagents that are potentially optimal for analyzing the PK of fully human antibodies that have been developed as therapeutic candidates. Indeed, anti-idiotype antibodies are usually combined with ELISA to detect the concentration of target antibodies. Compared with drug target capture, anti-idiotypic antibody bridging reduced the false positive rate significantly due to the high specificity of reagents.

Fig.2 Drug target capture and detection with anti-idiotypic antibodies.^2,4

Up to now, we have developed three mature approaches in developing anti-idiotypic antibodies: immunized phage display library technology, premade non-immunized human phage display library technology, and hybridomas technology, both of which can be applied to discover available anti-idiotypic antibodies for PK Assay. Our anti-idiotypic antibodies have advantages of single epitope, good specificity, good stability between batches.

At Creative Biolabs, we offer PK assay services tailored to biosimilar drugs, providing development for the drug's variable region or utilizing existing ADA products. For monoclonal antibodies, we develop single or paired anti-idiotypic antibodies targeting the variable region, while for bispecific antibodies, we create pairs targeting the variable regions of both parent antibodies. In the realm of ADCs, we produce anti-idiotypic antibodies against both the variable region and small molecules, and for nanobodies or scFvs, we offer single or paired antibodies against the entire antibody's variable region.

Advantages of Anti-ID Antibody for PK Assay

• Efficient and Economical: Our anti-idiotypic antibody discovery service for PK assays offers prompt responses with dedicated project team support, ensuring real-time tracking and updates of experimental progress.
• Sensitivity and Consistency: We develop antibodies with exceptional sensitivity and reproducibility, guaranteeing consistent and dependable results across varied experimental setups.
• Strong Binding Affinity: Our antibodies, characterized by robust binding affinity, enhance the precision and effectiveness of PK assays through stable interactions with target molecules.
• Professional Expertise: We supply essential reagents for PK and ADA analyses across a spectrum of drug types, including monoclonal and bispecific antibodies, ADCs, and CAR-T therapies.
• Comprehensive Functionality: From antigen preparation to the development of monoclonal and polyclonal anti-idiotype antibodies, as well as PK and immunogenicity test kits, we provide an all-encompassing service.
• Regulatory Compliance: Our PK and ADA test kits are delivered with sensitivity levels that meet stringent regulatory standards, ensuring reliability and compliance.

Anti-idiotypic antibody based PK assay is widely used in pre-clinical research. Creative Biolabs provides customized one-stop services for anti-idiotypic antibody production. For more details please feel free to contact us.

Published Data

Fig.3 Identification of anti-idiotypic antibody targeting anti-Dengue virus antibody.^{3, 4}

Anti-idiotype monoclonal antibodies, are invaluable in pharmacokinetic studies of fully human antibodies targeting high-biosafety pathogens. E1 was developed via phage display technology to detect an antibody candidate against Dengue virus. This recombinant anti-idiotype is highly specific to the native conformation of anti-Dengue virus antibody and facilitates its detection in human serum using ELISA. Moreover, E1 effectively blocks the binding of anti-Dengue virus antibody to Dengue virus serotype 1 and can trace its presence in mouse serum in vivo. Thus, E1 aids in monitoring therapeutic antibody candidates in clinical trials.

References

1. López-Requena, Alejandro, Oscar R. Burrone, and Michela Cesco-Gaspere. "Idiotypes as immunogens: facing the challenge of inducing strong therapeutic immune responses against the variable region of immunoglobulins." Frontiers in oncology 2 (2012): 159. Distributed under Open Access license CC BY 3.0, without modification.
2. Qin, Qiuping, and Likun Gong. "Current Analytical Strategies for Antibody-Drug Conjugates in Biomatrices." Molecules 27.19 (2022): 6299.
3. Lim, She Yah, et al. "The molecular engineering of an anti-idiotypic antibody for pharmacokinetic analysis of a fully human anti-infective." PLoS One 10.12 (2015): e0145381.
4. Distributed under Open Access license CC BY 4.0, without modification.

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