Masterarbeit zu vergeben – Virologie

An der Sektion für Virologie (Peter Mayr Str 4b) ist ab sofort eine Stelle für eine Masterarbeit frei.

In situ production of anti-CD20 antibodies with improved CDC to treat CLL

AAV vectors show low immunogenicity, are well tolerated by the host and are widely used as delivery vector in gene therapy. Thus, AAV-vectors are in several clinical trials to treat genetic deficiencies such as hemophilia or spinal atrophy of the muscles. A new aspect in this context is the use of AAV-vectors as tumor therapy using AAV vectors, which encode for tumor-specific but modified antibodies. The modification contains sequences, which enhance the complement response against tumor. For a proof of concept, we plan to target cells of patients with chronic-lymphatic leukemia (CLL). CLL is the most common form of Leukemia. It is characterized by the accumulation of B-cells leading to immunological defects. Treatment of choice is a combination of drugs and monoclonal antibodies (mAb). Ofatumumab (OFA) is such a mAb directed against CD20 expressed on the malignant cells. The efficacy of OFA is based on two main mechanisms, antibody-dependent cytotoxicity and complement-dependent cytotoxicity (CDC).
Unfortunately, CDC is not very effective, as CLL cells bind negative regulators of the complement system and block thereby CDC. We aim to modify OFA with sequences of that inhibit the binding of complement regulators on CLL cells and thereby enhance CDC significantly. Successful testing of the approach described above should provide the basis for the use AV-vectors to treat CLL.

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