Bispecific Antibody recognized Anti-Idiotypic Antibody Discovery Service

Overview of Our Services

Bispecific antibodies (BsAbs) combine the specificities of two antibodies and simultaneously address different antigens. With this 'two-target' function, BsAb can interfere with multiple surface ligands associated such as cancer, proliferation, or inflammatory processes. While the first BsAb was approved in 2009, BsAbs represent a key component of the next generation of antibody therapy with the current biotherapeutic market dominated by antibody molecules. Hence, the anti-idiotypic antibodies targeted to BsAbs which can bind two different domains are necessary for BsAb research. To date, various commercialized technology platforms are applied for anti-idiotypic antibody creation and production while a few of them are available for dual functional antibodies aimed at BsAb. Therefore, Creative Biolabs has established mature BsAb-binding anti-idiotypic antibody production platforms and launched related products. Moreover, based on our rich experience and skilled groups, we provide commercial and customized one-stop anti-idiotypic antibody production services to support your novel therapeutic molecule research and discovery.

Fig. 1 Architecture of common BsAbs formats.^{1, 4}

Introduction of BsAb

Antibodies with two different antigen-binding sites in one molecule are called bispecific antibodies (BsAbs), which were first reported in the 1960s. Most natural antibodies are multivalent molecules comprising identical antigen-binding sites, hence the BsAbs are generated by biochemical, molecular, or genetic means. Two common formats of bispecific antibodies on the market are the single-chain variable fragment (scFv) antibody and the full-length IgG-like asymmetric antibody. Nowadays, BsAbs are primarily produced by chemical conjugation, quadroma technology based on the somatic fusion of two different hybridoma cell lines, and recombinant DNA technology.

Fig. 2 Examples of mechanisms of action of BsAbs.^{1, 4}

Advantages of BsAb-binding Anti-ID Antibody

BsAbs are antibodies created through genetic engineering, possessing two distinct antigen-binding sites that target different epitopes or antigens. In comparison to monospecific antibody drugs, BsAbs are more prone to challenges such as proteolysis, aggregation, and physical instability. Additionally, simultaneous binding of the two antigen-binding sites to their respective ligands can result in significant steric hindrance. These complexities make it particularly challenging to screen anti-idiotypic antibodies that target various antigen-binding epitopes of bispecific antibodies.

Creative Biolabs has successfully executed multiple projects involving the development of anti-idiotypic antibodies that recognize BsAb drugs. The resulting anti-idiotypic antibodies can selectively bind to the two distinct antigen-binding sites with high specificity. Furthermore, we have screened both neutralizing and non-neutralizing anti-idiotypic antibodies against the monospecific units of BsAb drugs. These antibodies were paired in a capture ELISA format, achieving high detection sensitivity and an optimal recovery rate of approximately 100% across varying concentrations in human serum.

Applications

During the past decades, we have seen a phenomenal evolution of BsAbs for therapeutic applications. Currently, over 70 different BsAb therapeutic antibodies exist, some of which were promoted into the clinical pipeline. However, the lack of detection methods restricts its development and clinical application. While ELISA is a mature and widely used method in protein research, the anti-idiotypic antibodies which can bind both sites of BsAbs are required as primary antibodies in the ELISA detection, which can avoid false-positive and enhance the affinity. Therefore, as a basic tool in BsAb research, bis-functional and specific anti-idiotypic antibodies production became an important step in BsAb therapeutic antibody development.

Fig.3 BsAbs in development and registered in cancer clinical trials.^{2, 4}

Service Highlights

• Superior-quality Antibodies: BsAb-binding anti-idiotypic antibodies with exceptional specificity and sensitivity tailored to your target of interest.
• Rapid turnaround: The production process can be completed in as little as approximately 3.5 months, contact our sales staff to get more detailed process time.
• Versatile drug application: Compatible with various drugs, including monoclonal antibodies, peptides, proteins, compounds, cell lines, DNA, among others.
• Comprehensive service: Offering end-to-end technical services, ranging from antibody development to preclinical research for therapeutic antibodies.
• Tailored solutions: Delivering customized experimental plans based on your unique requirements, optimizing both time and cost efficiency.

Published Data

Fig.4 Biparatopic binding confirmation of anti-MET BpAb via ELISA, SPR and FACS assays.^{3, 4}

The development of bispecific antibodies is complicated by production challenges. This study introduces a dual anti-idiotypic purification method that yields bispecific antibodies with native immunoglobulin structures. Using camelid single-domain antibody fragments, a biparatopic IgG1 antibody targeting two unique non-overlapping epitopes on the MET receptor was purified. Mass spectrometry and binding assays confirmed the antibody’s dual targeting capability, enhancing MET inhibition compared to parental antibodies. This method demonstrated superior biological activity in vitro and in a tumor xenograft model, offering an innovative and effective strategy for producing highly pure and functional bispecific antibodies.

With the development of BsAb in the application in clinic treatment, the mature platforms to discover and product novel anti-idiotypic for BsAb is important. If you are interested in our anti-idiotypic antibody production of BsAb services, please feel free to contact us. You can also click here to see more custom anti-idiotypic antibodies production services from Creative Biolabs to meet your specific requirements.

References

1. Kang, Jingyue, Tonglin Sun, and Yan Zhang. "Immunotherapeutic progress and application of bispecific antibody in cancer." Frontiers in Immunology13 (2022): 1020003.
2. Suurs, Frans V., et al. "A review of bispecific antibodies and antibody constructs in oncology and clinical challenges." Pharmacology & therapeutics 201 (2019): 103-11
3. Godar, Marie, et al. "Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy." Scientific Reports 6.1 (2016): 31621.
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.