Antibody Therapeutics Industry Growth
In the dynamic fields of biotechnology and pharmaceutics, there is a rapid expansion from monoclonal antibodies to advanced modalities like bispecific and multispecific antibodies, single domain antibodies, and antibody-drug conjugates (ADCs). These next-generation antibody drugs and new modalities are seeing an unprecedented increased demand. According to Evaluate, a market intelligence firm, the ADC market will continue to grow in oncology, reaching $30B by 2028.1
The Need for High-Throughput Discovery
- Higher demand for faster production and testing methods with the rise of complex diseases such as cancer, autoimmune disorders, and infectious diseases to target various molecular pathways and biomarkers
- Competition among researchers and pharmaceutical companies to develop antibodies targeting the same disease indication
- A need to produce and test a larger number of antibody samples in a high-throughput fashion to increase the likelihood of finding therapeutically effective antibodies
- Importance of maintaining quality while accelerating the antibody discovery process to ensure the development of safe and efficacious therapeutics
- A desire for quicker discovery and shorter project turnaround times to address urgent medical needs and an aging population
1. Alpaca VHH Antibody Discovery Platform
Camelid single domain antibody (VHH) has been increasingly regarded as a valuable and versatile component for next-generation multispecific antibody therapeutics and cell therapies. The application of these alpaca or llama VHH also makes the animal-based antibody discovery platforms perform at an expedited pace when it’s combined with phage display technology. Depending on the target, companies can use purified proteins, DNA, over-expressing target cell lines, or a hybrid of these methods to immunize and achieve optimal serum antibody titer levels in naïve alpaca with trackable records.
An immunized phage library using PBMC samples can be quickly and efficiently constructed for phage panning since VHH is single chain without the concern of H/L chain matching. Typically, a ~109 library can be obtained with high CDR diversity. Solid-phase and solution-based phage panning are commonly used, often in parallel or in combination, to select antigen-specific binders. Once the VHH binders are screened, confirmed, and sequence identified, Biointron's proprietary high-throughput mammalian cell expression platform produces VHH candidates in under 2 weeks to provide mg-scale purified samples for further characterization – first with ELISA and/or FACS binding validation and often followed by SPR affinity determination, epitope binning, and preliminary functional assays.
2. Single-B Cell Antibody Discovery Platform
Single-B cell platforms are often developed based on three types of technologies: nanowell, microfluidic, and nanovial. Among these, microfluidic technology has been applied to related research in single-cell genetics, epigenetics, transcriptomics, proteomics, and metabolism. Additionally, it has the potential to achieve higher throughput and greater flexibility.
Compared to other methods for antibody discovery, single-B cell technology shows several advantages. Hybridoma technology is low-throughput and requires a timeline of 4-6 months. Bacterial phage display can perform at high-throughput and is more efficient at only 3-4 weeks, but it could have a higher rate of clones with developability issues and /or produce antibodies that possess unnaturally paired light and heavy chains. Single-B cell technology, when applied to antibody discovery, however, is both high-throughput and can allow the identification of antibodies with paired light and heavy chains in 1-2 weeks.
The single-B cell sorting process at Biointron (www.biointron.com) begins with sample preparation. Once mice are immunized with immunogen, B cells positive-selected with microbeads are distributed singularly in droplets containing binding reagents and antigens, such as directly labeled protein targets or cells expressing specific targets. These droplets are then cultured to allow binding to happen. Sorting can be done to identify droplets containing single cells with a positive binding signal. Combined with NGS sequencing and HTP antibody production, this antibody discovery platform can generate diverse, high-affinity antibodies against multiple epitopes within 2-3 months and has the potential to accelerate therapeutic development for a broad range of targets – including challenging transmembrane protein targets such as GPCR.
Key Benefits to Biopharma
- High-throughput antibody production platforms combine automated screening with recombinant DNA technologies
- Drastically reduces time required from gene synthesis to antibody production
- Critical in addressing urgent medical needs such as emerging infectious diseases and fast-developing cancers
- Increases likelihood of discovering therapeutics with superior specificity and potency
- Cost savings in the long run by reducing the time and resources needed for antibody discovery and development, ultimately speeding up the translation of research into clinical applications
Biointron's Expertise
In this landscape of evolving possibilities, Biointron stands out as an unparalleled choice as a leading high-throughput recombinant antibody/protein expression and discovery service provider. The company has over 12 years of experience focusing solely on antibody production. From gene sequence to purified antibodies, it just takes 2 weeks from sequence to purified recombinant antibody. Biointron has delivered tens of thousands of recombinant antibodies for more than 1,500 biotech and pharma companies all over the world.
Curious to learn more about antibody production?
Visit Biointron’s Learning Center or contact our expert team at info@biointron.com or +1 (732) 790-8340.
References
- Evaluate (2024) Antibody Drug Conjugates Report. Available at: https://www.evaluate.com/thought-leadership/antibody-drug-conjugates-report/.