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Fine Tuning Antibody Conjugation Methods using SNAP-tag Technology

: Chouman, K.; Woitok, M.; Mladenov, R.; Kessler, C.; Weinhold, E.; Hanz, G.; Fischer, R.; Meinhold-Heerlein, I.; Bleilevens, A.; Gresch, G.; Haugg, A.M.; Zeppernick, F.; Bauerschlag, D.; Maass, N.; Stickeler, E.; Kolberg, K.; Hussain, A.F.


Anti-cancer agents in medicinal chemistry 17 (2017), Nr.10, S.1434-1440
ISSN: 1875-5992
ISSN: 1871-5206
Fraunhofer IME ()

BACKGROUND: Targeted imaging and therapy (theranostics) is a promising approach for the simultaneous improvement of cancer diagnosis, prognosis and management. Therapeutic and imaging reagents are coupled to tumor-targeting molecules such as antibodies, providing a basis for truly personalized medicine. However, the development of antibody-drug conjugates with acceptable pharmaceutical properties is a complex process and several parameters must be optimized, such as the controlled conjugation method and the drug-to-antibody ratio. OBJECTIVE: The major aim of this work is to address fundamental key challenges for the development of versatile technology platform for generating homogenous immunotheranostic reagent. METHOD: We conjugated the theranostics reagent IRDye700dx to a recombinant antibody fusion protein containing a self-labeling protein (SNAP-tag) which provides a unique reaction site. RESULTS: The resulting conjugate was suitable for the imaging of cancer cells expressing the epidermal growth factor receptor and demonstrated potent phototherapeutic and imaging activities against them. CONCLUSION: Here, we describe a simple, rapid and robust site-directed labeling method that can be used to generate homogeneous immunoconjugate with defined pharmacological properties.