Fine Tuning Antibody Conjugation Methods using SNAP-tag Technology.

Abstract:

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.

authors

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

doi

10.2174/1871520617666170213123737

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

1434-1440

issue

10

eissn

1871-5206

issn

1875-5992

pii

ACAMC-EPUB-81724

journal_volume

17

pub_type

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