Construction and functional comparison of new antibody-based formats with multiple specificities for the exploration of innovative therapeutic approaches

Diplôme Thèse Construction and functional comparison of new antibody-based formats with multiple specificities for the exploration of innovative therapeutic approaches eng 2014-09-26 author Mueller Ulrike 670867 director Loewith Robbie Joséph 630703 director Magnenat Laurent 10.13097/archive-ouverte/unige:48392 urn:nbn:ch:unige-483920 Sc. 4734 Bispecific antibodies are capable of binding to two different antigens or to two distinct epitopes on the same antigen, the latter called biparatopic antibodies. Their dual specificity enables completely new therapeutic strategies and applications which were not achievable with the classical monoclonal antibody format. In this work, we constructed and comparatively characterized new antibody-based formats with multiple specificities, based on Dual-Variable-Domain Immunoglobulins, Strand Exchange Engineered Domains, and the IgG-scFv format, for two different innovative applications. The first part of the thesis work was dedicated to the development of novel biparatopic antibodies against granulocyte-macrophage colony stimulating factor and the investigation of their efficiency on the monomeric soluble target. The aim of the second part of the thesis was T cell immunomodulation through receptor co-ligation. Bispecific antibodies binding the T cell receptor as well as the inhibitory receptor PD-1 have been generated and characterized in vitro in relevant bioassays. Antibody engineering Biparatopic antibodies GM-CSF Bispecific antibodies Immunomodulatory antibodies PD-1 Dewey 570 43 Département de biologie moléculaire 161 false 91aaf36a-73bc-4726-ae03-325a02984eed Thesis Restricted Ulrike.pdf 5123684 application/pdf Private 2019-09-17 163e75568a27ad0fae80d7671882674e93c06d0bcb680961addf439275dd8425 restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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Construction and functional comparison of new antibody-based formats with multiple specificities for the exploration of innovative therapeutic approaches				2014	895	1

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Mueller, Ulrike