Magic™ Antibody Repertoire Analysis

Background Advantages Services Published Data Resources

Creative Biolabs offers our clients an amazing high-throughput sequencing and protein expression platform to analyze antibody repertoires for full length natively paired antibodies. Our platform integrates next generation sequencing (NGS) and bioinformatics in parallel, which can sequence the diverse antibody repertoire at a rate of millions of clones per hour. It can be applied to enhance the understanding of immunology and to revolute the traditional drug discovery process to meet the unmet clinical needs of infectious diseases, immune dysregulation, and cancer.

Background

Antibodies have important roles in protective and pathogenic immune responses. They are major components of the potent adaptive immune system. In response to microbial infection, autoimmune disease, cancer, or vaccination, the immune system generates a diverse antibody repertoire, which is continuously shaped by exposure to exogenous antigens and endogenous host factors. Analysis of these antibody repertoires, particularly those contributing to functional immune responses, can provide important information on protective and pathogenic immunity, while also furnishing insights into the underlying mechanisms of disease. Furthermore, in infectious diseases, there is growing interest in isolating and characterizing antibodies that could be developed as novel therapeutic agents or vaccines due to the antibody response.

Existing mechanisms for antibody diversification can yield an astronomical number of possible antibodies (in theory, over 10¹³ in humans). It is completely impractical to analyze such a diverse repertoire using traditional Sanger sequencing. Whereas the development of high-throughput DNA sequencing technologies enables large-scale characterization of functional antibodies and allows us to determine antibody gene repertoires at unprecedented depth.

Advantages of the Magic™ Platform

Creative Biolabs offers a high-throughput Magic™ platform for large scale sequencing of antibody repertoires using NGS combined with other techniques, such as expression and isolation of antigen-specific antibodies and proteomic analyses of antibodies in blood or secretions. This powerful platform can provide a high-fidelity analysis of the full-length paired heavy and light chains expressed by individual B cells, which is critical for characterizing functional antibody repertoires. In addition, through bioinformatics identification of clonal antibody families and recombinant expression of representative members, we can produce recombinant antibodies that can be used to identify the antigen targets of functional immune responses and to investigate the mechanisms of their protective or pathogenic functions.

Our unique platform can help elucidate the properties of antibodies that mediate protection against infectious diseases or, alternatively, that mediate autoimmune responses. Furthermore, this platform can be applied to advance our understanding of immunology and identify therapeutic, diagnostic, or mechanistic antibodies relevant to infectious diseases, autoimmune diseases, and cancer.

Magic™ Antibody Repertoire Analysis Services

Creative Biolabs has rich experience in the field of antibody repertoire analysis. We are confident in our ability to provide top-quality service to facilitate therapeutic antibody development.

Optional antibody fragment repertoire analysis services:

Fig. 1 Methods for high-throughput sequencing of the Ig sequence repertoire. (George Georgiou, 2014)

Published Data

Analysis of B Cell Antibody Repertoires

Fig. 2 Patient-derived antibody heavy and light chain cloning and production of recombinant human IgG1. (Silvia Crescioli, 2023)

B cells can accumulate at the edge of the tumor, infiltrate the tumor focus, or form structures from small cell aggregates to more organized tertiary lymphoid structures (TLS), indicating that B cells may greatly affect the immune response, thus affecting the progression of cancer and the outcome of treatment. In this study, scientists conducted a comprehensive assessment of memory and class-switched B cells, including B cell phenotype, antibody repertoire, and the specificity of humoral immune responses to metastatic cutaneous melanoma. The circulating and tumor resident B cells in metastatic cutaneous melanoma were deeply analyzed by cell subsets and antibody repertoires. Antigens were found in serum samples of patients with melanoma, and the recombinant antibodies derived from tumor resident IgD memory and total B cells were characterized. This study provides a new perspective on the abnormal properties of B cell phenotype, antibody repertoire, and specificity. These abnormal properties shape the humoral immune response in metastatic cutaneous melanoma and emphasize the autoimmune characteristics of cloned and expanded B cell banks.

References

Georgiou, G., Ippolito, G., Beausang, J. et al. The promise and challenge of high-throughput sequencing of the antibody repertoire. Nat Biotechnol 32, 158–168 (2014). https://doi.org/10.1038/nbt.2782
Crescioli, S., Correa, I., Ng, J. et al. B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma. Nat Commun 14, 3378 (2023). https://doi.org/10.1038/s41467-023-39042-y