Immune Checkpoint Antibody Discovery

Immune checkpoint inhibitors

As a kind of cancer immunotherapy, immune checkpoint inhibitors therapy is able to inhibit immune checkpoint functions resulting in down-regulating immune responses. In 2011, FDA approved the first immune checkpoint inhibitor which was Ipilimumab, a CTLA4 blocker, representing the possible application of immunotherapy in cancer therapy. And in 2014, FDA approved another two immune checkpoint inhibitors which are Pembrolizumab and Nivolumab, PD-1 antibodies, indicating that cancer immunotherapy becomes the fourth method for cancer therapy following by surgery, radiotherapy and chemotherapy.

Figure 1. Mechanism of PD1/PD-L1 antibodies. (NIH, 2015)

Currently approved immune checkpoint inhibitors

Immune checkpoint antibody discovery service

Current approved immune checkpoint inhibitors achieve huge success because of strong market demand by IP protection and market penetration strategies. During these years, Creative BioMart has focused on the research study of immune checkpoint antibodies, and we are devoted to provide superior immune checkpoint antibody discovery service to our customers for their immune checkpoint research study and industrial production. We deliver high quality immune checkpoint antibodies with good biological efficacy, safe and manufacturability to customers, and provide one-stop immune checkpoint antibody discovery service from targets to therapeutic antibody candidates to customers in around 12 months.

Figure 2. Flow of immune checkpoint antibody discovery service.

Immune checkpoints antigen Prep

For the targets to produce antibodies, there are four types which can be selected including DNA, peptide, protein, cell & combination.

Discovery technologies for antibody lead generation

There are mainly two technologies supplied in Creative BioMart, Hybridoma technology and Bispecific antibodies, respectively.

Hybridoma technology is an important method for producing large amounts of monoclonal antibodies and is a critical procedure for therapeutic mAb discovery and immune checkpoint antibody drug lead generation. The advantages of our technology:

• We own more than 100 high quality clonal hybridomas which can be performed on high throughout ELISA screening
• We have comprehensive functional assay for in vitro screening

Bispecific antibodies are a kind of antibodies which can simultaneously bind two separate antigens or different epitopes of the same antigen and they have been becoming more and more important in therapeutic applications. The benefits of bispecific antibodies include:

• Safety improvement because low off-target binding reduces side effects
• Price controlling because developing only one molecule but saving half of investment compared with combination therapy

Antibody lead characterization tool

There are two main tools included in this part, Biochemical & Biophysical assays and In vitro functional assays. Bio-analytics is essential in immune checkpoint antibody discovery, so we are devoted to provide biophysical, biochemical and functional analysis tools for antibody lead characterization.

The strengths of our antibody lead characterization include two parts. One is we have already developed more than 60 bioanalytic methods, another is that the largest HTS capacity of us is nearly 8000 molecules/day.

Biochemical assays

• Epitope mapping
• Antibody sequencing
• Affinity measurement

Antibody lead optimization

In this step, there are three dimensions included, antibody humanization, developability assessment and antibody affinity maturation, respectively. Antibody humanization is a vital procedure in immune checkpoint antibody discovery process because it can reduce immunogenicity of monoclonal antibodies derived from xenogeneic origins and improve immune checkpoint antibody activation in human immune system.

In vivo efficacy, exploratory PK and toxicity studies

The purpose of this step is to optimize immune checkpoint antibody lead with better biological efficacy and safety.