News Column

Findings from G. Badescu et al Update Understanding of Immunoglobulins (Bridging Disulfides for Stable and Defined Antibody Drug Conjugates)

July 23, 2014



By a News Reporter-Staff News Editor at Biotech Week -- A new study on Immunology is now available. According to news originating from London, United Kingdom, by NewsRx correspondents, research stated, "To improve both the homogeneity and the stability of ADCs, we have developed site-specific drug-conjugating reagents that covalently rebridge reduced disulfide bonds. The new reagents comprise a drug, a linker, and a bis-reactive conjugating moiety that is capable of undergoing reaction with both sulfur atoms derived from a reduced disulfide bond in antibodies and antibody fragments."

Our news journalists obtained a quote from the research, "A disulfide rebridging reagent comprising monomethyl auristatin E (MMAE) was prepared and conjugated to trastuzumab (TRA). A 78% conversion of antibody to ADC with a drug to antibody ratio (DAR) of 4 was achieved with no unconjugated antibody remaining. The MMAE rebridging reagent was also conjugated to the interchain disulfide of a Fab derived from proteolytic digestion of TRA, to give a homogeneous single drug conjugated product. The resulting conjugates retained antigen-binding, were stable in serum, and demonstrated potent and antigen-selective cell killing in in vitro and in vivo cancer models."

According to the news editors, the research concluded: "Disulfide rebridging conjugation is a general approach to prepare stable ADCs, which does not require the antibody to be recombinantly re-engineered for site-specific conjugation."

For more information on this research see: Bridging Disulfides for Stable and Defined Antibody Drug Conjugates. Bioconjugate Chemistry, 2014;25(6):1124-1136. Bioconjugate Chemistry can be contacted at: Amer Chemical Soc, 1155 16TH St, NW, Washington, DC 20036, USA. (American Chemical Society - www.acs.org; Bioconjugate Chemistry - www.pubs.acs.org/journal/bcches)

The news correspondents report that additional information may be obtained from G. Badescu, PolyTherics Ltd, London Biosci Innovat Center, London NW1 0NH, United Kingdom. Additional authors for this research include P. Bryant, M. Bird, K. Henseleit, J. Swierkosz, V. Parekh, R. Tommasi, E. Pawlisz, K. Jurlewicz, M. Farys, N. Camper, X.B. Sheng, M. Fisher, R. Grygorash, A. Kyle, A. Abhilash, M. Frigerio, J. Edwards and A. Godwin (see also Immunology).

Keywords for this news article include: Ions, Antibodies, London, Europe, Disulfides, Immunology, Electrolytes, United Kingdom, Blood Proteins, Immunoglobulins, Inorganic Chemicals

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Biotech Week


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