Conjugation of chemotherapeutics and diagnostic radionuclides to antibodies in a drug/antibody ratio of 4:1 enhances the therapeutic efficacy of the antibodies to optimum effect. Chemical modification of proteins gives heterogeneous populations with uncontrolled stoichiometries.
Roger Schibli and colleagues, ETH Zürich, Switzerland, have used bacterial transglutaminase (BTG) for the preparation of immunoconjugates functionalized with metal chelators and labeled with radionuclides.
For the chCE7agl conjugates tested, mass spectrometry revealed two modifications of the HC in all substrates, giving optimal stoichiometry. In vivo testing of the uptake behavior of BTG-modified conjugates showed mean uptake into human ovarian carcinoma xenografts was 58.7 % IDg–1 after 72 h compared with a maximum uptake of 21.0 % IDg–1 at 48 h for a chemically prepared analogue.
This method is broadly applicable and could lead to a range of immunoconjugates with optimum stoichiometries for the imaging and treatment of cancer.
- Site-Specific and Stoichiometric Modification of Antibodies by Bacterial Transglutaminase
S. Jeger, K. Zimmermann, A. Blanc, J. Grünberg, M. Honer, P. Hunziker, H. Struthers, R. Schibli,
Angew. Chem. Int. Ed. 2010.
- S. Jeger, K. Zimmermann, A. Blanc, J. Grünberg, M. Honer, P. Hunziker, H. Struthers, R. Schibli
Angew. Chem. 2010.