Internalizing Antibody Engineering

Creative Biolabs is a leader in developing internalizing antibodies to facilitate various downstream applications, including the development of antibody-drug conjugate, intracellular targeting bispecific antibody, intrabody, etc. With extensive experience in antibody engineering and modification, Creative Biolabs is dedicated to serving as your one-stop service provider for internalizing antibody development projects.

Antibodies internalize into the targeted cells via receptor-mediated endocytosis. In this process, the antibodies function as ligands that interact specifically with cell surface targets, which subsequently undergo a clathrin-dependent internalization pathway and are trafficked into various subcellular localizations.

Figure 1. The general pathway of receptor-mediated endocytosis (RME). Extracellular ligands (antibodies in this case) interact with cell surface receptors. The complex is then transferred inside the cell via vesicles and re-directed to various intracellular locations.

Typical Applications of Internalizing Antibodies

Internalizing antibodies have exceptional potentials to serve as the next generation immunotherapeutic agents. Taking antibody-drug conjugate (ADC) as an example, the antibody portion of an ADC is not only the guidance system to accurately locate cancer cells, but more importantly, it mediates the internal release of the toxic payload via internalization. Internalization has become a prerequisite in ADC design and heavily relied on the payload release mechanisms. Another field under active exploration is bispecific antibodies targeting intracellular targets. Internalization is achieved via one arm of the bispecific antibody to enable the intracellular tracking and targeting of the desired antigen target.

General Engineering Processes to Enhance Internalization Capacity

Common antibody development platforms, including hybridoma, phage display antibody library screening, and plasma cell sorting, can yield internalizing antibodies. Creative Biolabs has established several internalization strategies to facilitate the screening and identification of such antibodies. In the meantime, antibody engineering and modification methods can also be used to generate antibodies with higher potential for internalization.

Through our internalization enhancement services, we can integrate the advantages of several engineering processes with internalization screening to improve or facilitate the internalization capacity of an existing antibody or develop new internalizing antibodies. For instance, the installation of the cell-penetrating peptides and glycan engineering to increase the susceptibility of antibodies to unique endocytosis pathways.

In some cases, antibody dissociation is required upon internalization to ensure the correct intracellular antibody trafficking. Through our featured intracellular dissociation engineering service, Creative Biolabs exploits the “His-scan” method to help create antibodies that exert high target binding affinity at physiological pH but undergo target dissociation once exposed to the acidic intracellular environment. The dissociation is important for retaining the antibodies in the correct endosome paths to reach their desired subcellular compartments.

Through decades of effort in antibody engineering, Creative Biolabs is experienced with the techniques to create antibodies with desired features. Using our advanced technical platforms, we are committed to helping our clients develop internalizing antibodies for various purposes. Please contact us for more information and a detailed quotation.

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.