Development of bispecific antibodies with optimized T cell costimulatory activity

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Dokumentart: Dissertation
Date: 2022-10-19
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Biologie
Advisor: Jung, Gundram (Prof. Dr.)
Day of Oral Examination: 2020-10-19
DDC Classifikation: 500 - Natural sciences and mathematics
570 - Life sciences; biology
Keywords: Antikörper , Immunologie , Immunbiologie , Tumorimmunologie , Immuntherapie , Proteindesign
Other Keywords: bispezifische Antikörper
therapeutische Antikörper
bispecific antibodies
Antibody engineering
License: Publishing license excluding print on demand
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Dissertation ist gesperrt bis 19. Oktober 2022 !


In recent years, the clinical application of therapeutic antibodies has already significantly improved the therapy and prognosis of various malignant diseases. Notably, immunomodulating antibodies demonstrated the possibility to selectively modify the T cell-response and thus represent an attractive therapeutic strategy. However, in many cases, the therapeutic success of monospecific antibodies is limited or comes with severe systematic side-effects in patients. In comparison, the use of bispecific antibodies demonstrated several advantages by enabling the recruitment and activation of effector cells such as T cells, specifically at the tumor side. This thesis presents the in-vitro generation, characterization, and optimization of novel immunomodulating bispecific antibodies for target cell-restricted modulation of T cell activation. The bispecific antibodies were subjected to an extensive characterization process aiming at the identification of the optimal antibody format and clone. Finally, secondary work focused on a successful humanization by CDR grafting to decrease the risk of immunogenicity. Taken together, certain immunomodulating antibodies described in this work demonstrated a beneficial effect on activated T cells only in a target cell-restricted manner and demonstrate the potential of a novel promising therapeutic candidate for selective cancer treatment.

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