Internalizing Receptor Enhancement Service

With over a decade of experience in antibody engineering and modification, Creative Biolabs is dedicated to using well-established methodologies for innovative science and promoting the field of therapeutic antibody development.

Receptor-Mediated Transbody

Antibodies are Y-shaped glycoproteins produced by the immune system that recognize and target corresponding antigens with high affinity and specificity. They are widely used nowadays in cancer immunotherapies through various mechanisms, including receptor activity modulation, receptor blocking, triggering immune responses (e.g. ADCC and CDC), and so on. One unique action mode of antibodies is to expedite receptor turnover by inducing receptor internalization upon interaction.

The core principle behind antibody-associated receptor internalization is receptor-mediated endocytosis (REM), a process that involves the protein “clathrin” and is often referred to as clathrin-dependent endocytosis (CDE). The receptor-ligand (antibody in this case) complexes are transported by vesicles into early endosomes where they undergo different transportation pathways along with the ER system and end up in various subcellular localizations.

The discovery and further study of REM opens a gateway into cancer cells and it brings upon a new horizon for the next-generation antibody development that can either bring a toxin into cancer cells to achieve discriminated cancer elimination (antibody-drug conjugates, ADCs), or disrupt cancer subcellular function by targeting an intracellular target (bispecific antibodies). To this end, transbody, which possesses desired internalization capacity, is an essential component for the development of those innovative approaches.

Enhancement of Internalization Capacity via Affinity Maturation

Collective evidence has indicated that the receptor-binding affinity is a key factor in receptor-mediated antibody internalization. Antibodies with higher affinity against tumor receptors often show more rapid internalization and lower tumor accumulation, while lower affinity antibodies exert good tumor accumulation and sometimes penetration. Bearing this principle, Creative Biolabs is able to utilize our well-developed affinity maturation strategy to screen internalizing antibodies with enhanced receptor-binding ability.

Creative Biolabs offers several methods to increase antibody affinity. Our scientists are experienced with error-prone PCR techniques and can create a full library of mutations by this untargeted mutagenesis approach. Alternatively, with the knowledge of the antibody/receptor complex structure and interaction pattern, we can perform more systematically design to conduct an oligonucleotide-directed mutagenesis approach. Based on our advanced phage display platform, our scientists can efficiently screen a large library of antibodies and identify the candidates with the highest binding affinity towards the receptor of interest. Through this affinity maturation strategy, we have successfully generated various antibodies bearing nM or even pM range affinity, which is high enough for internalization.

Fig.1 A schematic representation of the affinity maturation process facilitated by phage display.¹

Creative Biolabs is your one-stop-shop for internalizing antibody discovery and development, we are committed to providing the scientific community with top-quality services to facilitate your project, which can also involve the development of ADC or bispecific antibodies targeting intracellular antigens. If you are interested in our transbody-related services, please feel free to contact us for more details.

Reference

1. Hu, Dongmei, et al. "Effective optimization of antibody affinity by phage display integrated with high-throughput DNA synthesis and sequencing technologies." PloS one 10.6 (2015): e0129125. Use under Open Access license CC BY 4.0, without modification.

Platform:

Intracellular Antibody Development Platform

All of our antibody products and services can only be used for preclinical research studies. Do not use them on humans.