Genmab A/S announced that its HuMax-CD20 human antibody appears to kill tumour cells that are resistant to rituximab, a marketed antibody directed to the same disease target. In pre-clinical testing, HuMax-CD20 effectively killed tumour cells from a number of cancer patients who had B-cell chronic lymphocytic leukemia (B-CLL). In side-by-side testing of killing in whole blood, HuMax-CD20 killed up to 50 per cent of the B-CLL tumours compared to no more than 5 per cent for rituximab.
In addition, HuMax-CD20 also effectively killed B-ALL cells from a cell line derived from a patient with B-cell acute lymphocytic leukemia. In side by side testing in whole blood, HuMax-CD20 killed up to 100 per cent of B-ALL cells compared to no more than 10 per cent for rituximab.
These data will be presented today at the Keystone Symposium "Antibody-Based Therapeutics for Cancer" in Banff, Alberta, Canada by Professor Jan van de Winkel, Chief Scientific Officer of Genmab.
Professor van de Winkel will also present data showing that recent discoveries about this type of cancer and also about HuMax-CD20 may help explain its ability to kill rituximab resistant cells. These patient tumour cells have very low levels of the CD20 target as well as a high level of cell surface proteins called complement control molecules that appear to protect cells from a type of immune system killing called complement dependent cytotoxicity. HuMax-CD20 may be overcoming the resistance because it binds to the CD20 target for a significantly longer period of time than rituximab.
HuMax-CD20 is currently undergoing manufacturing development in preparation for clinical trials.
Professor van de Winkel will also present new data showing that HuMax-EGFr effectively engages immune effector mechanisms. A combination of laboratory and animal disease model results show that HuMax-EGFr interrupts the cell signaling that causes tumour growth, causes tumour cell killing by antibody dependent cellular cytotoxicity, blocks the binding of growth factors to tumour cells and directly slows the rate of tumour growth. HuMax-EGFr is also undergoing manufacturing development in preparation for clinical trials.
"HuMax-CD20 is one of our key focus programs for 2003, and we are very encouraged by this set of biological data" said Lisa N. Drakeman, Ph.D., chief executive officer of Genmab. "The range of diseases we could potentially treat with HuMax-CD20 indicates the large market potential for this antibody."
"The pre-clinical data for both HuMax-CD20 and HuMax-EGFr shows that by using our cutting-edge technology we can effectively generate antibodies that out-perform earlier cancer therapeutic antibodies", said Professor van de Winkel. "Our antibodies exhibit better binding characteristics, and appear to be far better in engaging immune effector mechanisms that are key for the therapeutic efficacy of anti-cancer antibodies."
HuMax-CD20 targets the CD20 antigen on B-cells and initially Genmab plans to focus on using the antibody for the treatment of Non Hodgkin's Lymphoma (NHL), a cancer involving B-cells. Antibodies targeting CD20 also have the potential to treat illnesses such as Inflammatory Bowel Disease, Wegener's Granulomatosis, other B-cell lymphomas, including mantle cell lymphoma and autoimmune diseases such as rheumatoid arthritis.
The CD20 antigen is a transmembrane protein on pre-B and mature B lymphocytes. CD20 appears to act as a calcium ion channel, and to regulate early steps in B lymphocyte activation. The molecule is not shed from the cell surface, and is not internalized upon antibody binding. CD20 is found on over 90 percent of B-cell lymphomas, as well as other lymphoid tumours of B cell origin.
HuMax-EGFr is a high affinity, fully human monoclonal antibody that targets the Epidermal Growth Factor receptor (EGF-R). This receptor is over-expressed on a number of malignant tumours, including head and neck cancer and colorectal cancer. Growth and survival of such tumours are linked to activation of this receptor. HuMax-EGFr inhibits the growth of cells and has shown to eradicate tumours in animal models.