Developing one-step site-specific antibody conjugation method using SNAP-tag technology

Antibody-based diagnostic and therapeutic agents play a significant role in medicine, especially in cancer management. A variety of chemical, genetic and enzymatic site-specific conjugation methods have been developed for equipping antibodies with effector molecules aiming to generate homogeneous antibody conjugates with tailored properties. However, most of these methods are relatively complicated, expensive and need several reaction steps.

To avoid these limitations we have developed a novel method that allows monovalent conjugation of antibodies with effector molecules with high efficacy under physiological conditions. Here, we have exploited the unique conjugation properties of SNAP-tag to develop a simple, controlled and robust site-specific conjugation method by genetically fusing SNAP-tag to different antibody fragments binding to tumor cell surface antigens.

Furthermore, we have developed a site-specific dual conjugation method which simultaneously yet independently allows the conjugation of two different effector molecules to an individual antibody fragments using SNAP-tag and CLIP-tag (sibling of the SNAP-tag).  This strategy allows to label scFv with two different effector molecules in a single-pot reaction.