The company says this new technology may enable the creation of virtually any multifunctional protein for diverse applications. For example, one potential application is to connect multiple antibody fragments with toxic drugs or radioisotopes for disease therapy or imaging.
Another possibility is to increase the circulation time of hormones, hematopoietic growth factors, or cytokines in the body by linking them to polymers or albumin. The method could also provide a novel means for selective targeting in gene therapy.
Termed the Dock and Lock (DNL) method, the technology is based on the exploitation of two alpha-helical peptides that are found in nature to bind specifically with each other. By recombinantly fusing or chemically attaching each peptide to a constituent of interest, these helices provide an excellent linker module for ‘docking’ the two modified components into a quasi-stable structure, which is further ‘locked’ into a stable complex.
To prove the validity of the technology, a new trivalent, bispecific protein, TF2, comprising three stably linked Fab fragments, was generated from two of Immunomedics’ humanized antibodies, hMN-14, which binds specifically to carcinoembryonic antigen (CEA), and h679, which recognizes the peptide-hapten, histamine-succinyl-glycine (HSG).
Pretargeting studies using TF2 and a technetium-99m-labeled HSG-radiotracer in a CEA-expressing human colon cancer growing in mice demonstrated that 30% of injected radiotracer was bound to tumor within one hour.