Creative Biolabs now offers high-throughput screening service of internalizing antibodies to our customers around the world. Integrated with multiple leading-edge technology platforms, we can guarantee our clients with the most efficient and reliable service to isolate antibody candidates with internalization potential against various membrane targets.
Receptor-mediated internalization is a critical characteristic of therapeutic antibodies. Upon binding membrane target, the antibody-receptor complex can initiatively translocate into the cytosol via endocytosis, resulting in either degradation or recycling (mostly FcRn-mediated). Fc-mediated antibody internalization is closely related to the antibody in vivo half-life; more importantly, Fv-mediated antibody internalization, as in most cases, can cause target receptor down-regulation on the cell membrane, thus eliciting diverse downstream therapeutic effects. Many of the most famous antibody drugs on the market have internalization potentials as one important mechanism of action.
In addition, antibodies with internalization functions can act as excellent vehicles for targeted delivery of drugs, toxins, enzymes or DNA into cells for many therapeutic/ diagnostic applications. In contrast to receptor-independent reagents that can penetrate cell membranes, receptor-mediated internalizing antibodies are able to confer cell-specific drug delivery, which is the fundamental requirement for targeted therapy, i.e. ADC. Notably, for this type of application, internalization abilities are sometimes cargo-dependent. An internalizing antibody/peptide that permits internalization of one cargo may not support the internalization of a different cargo. Therefore, custom cargo-fusion antibody libraries are very necessary.
Equipped with state-of-the-art technical platforms and vast expertise in antibody development field, Creative Biolabs provides multiple options for pursuing internalizing antibodies towards given surface receptor:
Phage Display Library Internalization Screening
We have done a large number of whole-cell based phage display library screening projects to select internalizing antibodies and peptides specific for various cell surface receptors such as EGFR, NTRK2, CTLA4, HER2, CD20, CD3, CD59, transferrin receptor, and CD33. Our staff scientists also have extensive experience in the discovery of novel marker receptors by selecting internalizing antibodies and peptides that are specific for certain cell types. Methodologies are developed to reduce the number of internalizing phage particles that do not target receptor-specific to exclude phage particles which are merely bound to the cell surface and to selectively identify phage particles that are capable of crosslinking receptors rather than merely binding.
Fluorogen Activating Protein
This innovative technology employs a novel reporter tag called fluorogen activated proteins (FAP) to genetically label the indicated membrane receptor, which can exhibit fluorescence after incorporation with particular soluble fluorogens. We successively apply two kinds of fluorogens with different binding ability and cell permeability. In this way, intracellular and extracellular tags can reveal different colors. Our simple, robust FAP-tag makes a powerful approach for high-throughput, dynamic studies of antibody/receptor internalization and trafficking.
GPCR Internalization Stable Cell Line
Creative Biolabs is professional in developing GPCR stable cell lines that are amendable to various applications, e.g. receptor function screening, affinity measurement, and internalization screening. In particular, by overexpressing indicated GPCR fused with fluorescent proteins, these engineered cell lines can assay or analyze compounds for their ability to induce receptor internalization. Single cells with strong intracellular fluorescence will be selected via FACS. Currently, there are over 100 GPCR internalization cell lines available in Creative Biolabs. New strains can also be constructed upon request.
Scientists in Creative Biolabs is specialized in tailoring the most suitable plans according to special custom demands and expectations. Please contact us for more information.