Hemibodies – a new antibody format for cancer immunotherapy
Dr. Thomas Bumm
University Hospital of Würzburg – Medical Clinic and Polyclinic II – Department of Haematology and Oncology
Recipient: University Hospital of Würzburg
Funding: GO-Bio Phase I (01.09.2016 - 28.02.2019, 3.336.564 Euro)
Cancer immune therapies exploit the power of T cells, the specialised components of the immune system that can attack and eliminate cancer cells. However, before T cells can become active assassins, they must first bind extremely precisely to the cancer cells. In leukaemia therapy, so-called bi-specific antibodies are already utilised extremely successfully to facilitate targeted binding. Here, a German-developed drug functions as a kind of molecular adapter, ensuring that T cells bind directly to cancer cells. To date, however, the use of these bi-specific antibodies has been restricted to just a few forms of cancer. In addition, a lack of specificity can sometimes result in severe side effects.
Now, the Würzburg-based team led by Gernot Stuhler and Thomas Bumm has developed an entirely new antibody format that can guide T cells even more precisely towards cancer cells. This is based on two incomplete antibody modules, each directed against a different target structure on the cancer cells. The concept behind the hemibodies: on the surface of a cancer cell, the two ‘half portions’ of the antibody unite to form a whole. In this ‘duet’, the antibody becomes functional and begins to pilot the T cells in the destruction of cancer cells. Thus, the combination drug only assembles locally at the site of the tumour, where it triggers a targeted immune reaction.
With the first phase of funding from GO-Bio, the team headed by Stuhler and Bumm at the University Hospital of Würzburg is planning the complete preclinical development of a hemibody pair against multiple myeloma, a currently incurable disease of the bone marrow. Production of myeloma-specific hemibodies according to GMP standards will be pursued in a subsequent stage. The hemibodies produced in this GMP process will be examined in detail with the intention of later use in a clinical phase I/II study within the scope of a second GO-Bio phase.