Research

A research focus of the working group is the evaluation, identification and characterization of new target structures, antibodies and antibody-based molecules for the treatment of multiple myeloma. Multiple myeloma is a blood cancer in which the plasma cells in the patient's bone marrow become malignant and lead to anemia, bone lesions and kidney damage in the mostly elderly patients. The tumor cells are often located in niches in the bone marrow, some of which protect them from the effects of certain therapeutic agents. In recent years, various immunotherapies such as monoclonal and bispecific antibodies, antibody-drug conjugates and chimeric antigen receptor (CAR) T cells have been approved for the treatment of multiple myeloma and have improved the survival of many, but unfortunately not all, patients. Therefore, the search for new target structures/antigens on the myeloma cells and the identification of antibody derivatives that are as tailor-made as possible for the treatment represent major challenges that the working group is investigating. A wide variety of in vitro assays with myeloma cell lines and primary patient cells are used for this purpose. Promising molecules are tested in vivo in mouse models. In addition, there is close cooperation for the development of immunotherapeutic approaches for hematological and solid tumor diseases with other research groups and industry. 

The Antibody Engineering group is working intensively on various strategies to improve the activation and recruitment of immune effector cells. To this end, the group has established technologies to equip antibody derivatives with tailored effector functions. In particular, natural killer cells, various T cell subpopulations and macrophages are the focus of this work. Since the number of immune cells in tumor tissue/tumor microenvironment is often limited or exhausted, we are also working on concepts for targeted local effector cell expansion and attraction. Another area of ​​research are so-called antibody-drug conjugates. In this area, our group works, for example, on the development of new substances for the therapy of acute leukemias, in particular acute T cell leukemia (T-ALL).

Various strategies established for cancer therapy can probably also be used to treat autoimmune diseases. Innovative new approaches to immunotherapy for autoimmune diseases represent a relatively new research area of the group.

In my PhD thesis, I am working on novel strategies to develop and optimize antibody therapies for Acute Lymphoblastic Leukemia (ALL). Fc-Engineering is one strategy to increase the antitumor efficacy of antibodies by improving Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC), which are crucial functions in antibody therapy of various tumors. The use of antibody-drug conjugates (ADC) represents another optimization of antibody therapies. By conjugating cytotoxic substances to monoclonal antibodies, the antitumor potential can be increased. Targeted binding of the antibody to tumor-associated antigens can attenuate the systemic toxicity of the coupled drugs and reduce side effects. In addition to generation, production, purification and biochemical characterization, I analysed these novel antibody-based immunotherapies with established tumor cell lines or patient cells in vitro as well as in vivo in xenograft mouse models.

The activity status of the immune system during various malignant diseases plays a critical role in patient prognosis. In patients, immune cells may become exhausted or the recognition of tumor cells by immune cells may be disrupted by various mechanisms. Therefore, this project focuses on expansion of immune cells and strategies to enhance their activity. One approach is to develop monoclonal antibodies/antibody fragments that expand/activate immune cells in vicinity to the tumor. In addition, fit-for-purpose antibodies are developed that activate immune cells and redirect them against tumor cells. The influence of the antibody architecture is investigated to identify favorable molecule parameters having a positive impact on antibody efficacy.

Pemphigoid diseases (PDs) are a group of organ-specific, antibody-driven autoimmune diseases. The produced autoantibodies target hemidesmosomal adhesion proteins of the dermal-epidermal junction (DEJ). PDs affect the skin and its adjacent mucous membranes and lead to severe skin inflammation and tissue injuries typically presenting as subepidermal blisters. Complement proteins C5 and C5a are key drivers of the pathogenesis of PDs. In my PhD, I am focusing on the development of novel antibody derivatives designed to act site specifically at the area of the DEJ as the site of action of both autoantibodies and immune effector cells to prevent the disruption of the DEJ.