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Anti-idiotype Antibody Production Services

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Creative Biolabs provides unparalleled custom anti-idiotypic antibody (anti-ID Abs) production and downstream assay services to support your study, preclinical and clinical trials and the development of monoclonal antibody drugs. Creative Biolabs is professional in developing high specificity and affinity monoclonal antibodies from various species (including rabbit, chicken, llama, camel, alpaca, cow, dog, mouse, rat, sheep and human). In addition to mouse and rat hybridoma production methods, we have phage display immune antibody library construction and screening methods which are the best method to raise monoclonal antibodies from species that do not have hybridoma technology available. We provide both custom anti-idiotypic antibody production services and products to meet our customers’ needs.

Anti-idiotype Antibody Production Services Figure 1. Antibody idiotope— the unique set of antigenic determinants of the variable region of an antibody. The idiotype represents the variable part of an antibody, including the unique antigen binding site, and the combination of epitopes within the idiotype (i.e., the idiotopes) is unique for each antibody (Figure 1). When one antibody binds to one idiotope of another antibody it is referred to as an anti-idiotypic antibody (anti-ID). These highly specialized anti-idiotypic antibodies can be used in a PK assay to measure the drug level in patient samples and as a positive control or reference standard in any immune response (IR) assay (Figure 2).

Anti-idiotype Antibody Production Services Figure 2. Image shows anti-ID full immunoglobulin in blue or green, drug target in red, drug in purple, anti-Fc antibody in gray, and HRP in yellow. (A) PK Assay Format 1: Antigen Capture Assay ; (B) PK Assay Format 2: Antigen Capture Assay with Complex-Specific Antibody; (C) PK Assay Format 3: Anti-Idiotypic Antibody Bridging Assay; (D) PK Assay Format 4: Anti-Idiotypic Antibody-Antigen Bridging Assay; (E) IR Assay: Anti-Idiotypic Antibody Bridging Assay.

Anti-idiotype Antibody Production ServicesFigure 3. Four types of anti-idiotypic antibodies.

Type 1. Anti-idiotypic antibody detecting FREE antibody. (paratope specific, inhibitory, neutralizing, detects free drug)
Type 2. Anti-idiotypic antibody detecting TOTAL antibody. (not paratope specific, not inhibitory, detects total drug)
Type 3. Drug-target complex specific antibody detecting BOUND antibody. (not inhibitory, detects bound drug exclusively)
Type 4. Anti-idiotypic antibody detecting T cell receptor.

Applications:
• Antibody drug pharmacokinetic/pharmacodynamics (PK/PD) studies: the anti-ID capture Sandwich ELISA and anti-ID antibody bridging
• Antibody drug immunogenicity (immune response, IR) studies
• Preclinical research of therapeutic antibodies
• Anti-drug antibodies (ADA) for clinical development
• Controls in ligand binding neutralizing assays
• Controls in antibody blocking assays

Three approaches in developing anti-idiotypic antibodies:

Immunized phage display library technology: 
Target antibody in the forms of whole IgG, scFv, Fab or F(ab’)2 or peptides designed according to the sequences of the variable domains is utilized to immunize animals. Isolated immunized antibody library is packaged to phage library and anti-ID antibodies can then be generated by biopanning for 3-4 cycles. scFv/Fab antibodies with an affinity of 10-10 M could be obtained. In vitro selection allows us to use  isotype-matching control antibodies as blockers, to avoid enrichment of antibodies that bind to other regions of the target antibody.

Premade non-immunized human phage display library technology:  Phage display technology in the absence of immunization suits perfectly for the conformational epitope targeting anti-idiotypic antibodies, since in vitro selection well maintains the correctly folded conformation of target antibody.

Hybridomas technology: 
scFv/Fab forms of target antibodies are utilized to immunize rats or mice in the presence of isotype matching control antibodies for counter-selection.

Guarantees:
• Fast turnaround time: 8 weeks
• More than 98% success rate
• High specificity and binding affinity
• Convert to full length immunoglobulin as required isotype
• Long-term, secure supply from preclinical research through to clinical testing
• Readily integrated downstream antibody drug PK/PD and immunogenicity assay development

Creative Biolabs provides custom anti-idiotypic antibody production including but not limited to:

Reference
Turner, A. (2014) 'Anti-Idiotypic Antibodies to Monitor Immune Responses', Genetic Engineering & Biotechnology News, 34(17).




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