by
Dr. Christian Klein
Roche Innovation Center Zurich
Wednesday October 5th, 2016, 12:15-13:00
Teknologibygget 1.022
The major challenge in the generation of bispecific IgG antibodies is enforcement of the correct heavy and light chain association. Various technologies have been developed during the last years to tackle this challenge. This presentation will review different technologies with a focus on CrossMAb technology. The correct association of generic light chains can be enabled using immunoglobulin domain crossover, known as CrossMAb technology, which can be combined with approaches enabling correct heavy chain association such as knobs-into-holes (KiH) technology or electrostatic steering. Since its development, this technology has proven to be very versatile, allowing the generation of various bispecific antibody formats, not only heterodimeric/asymmetric bivalent 1+1 CrossMAbs, but also tri- (2+1), tetravalent (2+2) bispecific and multispecific antibodies. Numerous CrossMAbs have been evaluated in preclinical studies, and, so far, 4 different tailor-made bispecific antibodies based on the CrossMAb technology have entered clinical studies.
Christian Klein is Head of Oncology Programs and Department Head Cancer Immunotherapy Discovery at the Roche Innovation Center Zurich, Roche Pharmaceutical Research & Early Development specialized in engineering of (bispecific) antibodies and the discovery, validation and preclinical development of antibody-based Cancer Immunotherapy. He has made major contributions to the development and FDA/EMA approval of GAZYVA/GAZYVARO (obinutuzumab, GA101), to the preclinical development of the bispecific Ang-2/VEGF CrossMAb RG7221 (vanucizumab), the CEA-IL2v (RG7813) and FAP-IL2v (RG7461) immunocytokines, and to the development of Roche's immunocytokine and T cell bispecific antibody platform including CEA TCB (RG7802). As a research project team leader he currently takes care of a number of novel preclinical stage antibody-based cancer immunotherapy projects.