Researchers at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) have developed antibodies against the cell surface protein BCMA that promise to heal multiple myeloma, a type of bone tumor that is at present incurable. The biotechnology company Heidelberg Pharma will now develop one of these antibodies to an antibody-toxin agent and test it clinically at the end of 2018. MDC and Heidelberg Pharma signed the underlying license agreement in January of 2017.
Multiple myeloma is the most common type of bone marrow tumor. The rapidly progressing disease is incurable and develops due to the degeneration of individual plasma cells, with their clones spreading in the bone marrow.
One approach to possible treatments for this disease is the cell surface protein BCMA, found in a high density on all plasma cells and abnormal cells of the multiple myeloma but not occurring on other somatic cells. This makes it an attractive target structure for the development of new, highly specific medications against multiple myeloma. According to the National Institutes of Health (USA), multiple myeloma is responsible for 2.1 per cent of all tumor-induced fatalities in the US.
In recent years, the researchers Uta Höpken, Stephen Marino, Gerd Müller, Felix Oden and Daniel Olal from the MDC research groups of Oliver Daumke and Martin Lipp developed a number of antibodies that bind the BCMA protein with very high specificity. The researchers could demonstrate their effectiveness in a mouse model of multiple myeloma.
MDC cooperated with Heidelberg Pharma in a pilot project: the company linked the MDC antibodies to the amanitin toxin of the death cap mushroom. The antibody delivers the toxin specifically to the cancer cells, thereby killing them. These newly developed antibody-active substance conjugates combine the specificity of the MDC antibodies with the effectiveness of amanitin. The toxin has a unique mode of action that overcomes the resistances of cancer cells and destroys both growing and dormant cancer cells.
The conjugates were tested in vitro and in vivo, with the most promising one (HDP-101) chosen for further development. In the mouse model, the tumor was fully repressed with only low doses of HDP-101.
“It fills me with joy and pride that antibodies developed at the MDC are now being used to realize a highly promising therapeutic agent for multiple myeloma. These kind of transfers from science to application that lead to advancements in medicine are a core task for the MDC and are especially important to me personally,” says Professor Dr. Martin Lohse, Scientific Director and Chairman of the Board at the MDC.
HDP-101 is already undergoing pre-clinical trials. Its use in the first clinical trials is planned for 2018.