Antibody BI-505 : possible treatment for MULTIPLE MYELOMA
06 May 2013
“We tested the antibody in various ways, including on tumour cells from myeloma patients that have been transplanted into mice. The tests showed that the antibody is able to destroy myeloma cells”, explains Markus Hansson, a researcher at Lund University in Sweden.
Using a ‘biological library’ of thousands of antibodies from the company BioInvent in Lund, the team singled out antibody BI-505, shown to have a powerful effect on the tumour cells in both cell studies and animal experiments. It has also been tested in an initial safety study on seriously ill patients, and a study of its treatment effects has just started.
“This study will include patients who have just been diagnosed and therefore still feel fairly well. We want to test the antibody treatment before the patients are treated with any other drugs”, says Markus Hansson.
Today there are a number of drugs to treat multiple myeloma, but no cure. None of the drugs are able to eradicate the disease, meaning cancer cells increase in number after a period of remission. Survival has been extended with new treatments, but less than half of all patients live longer than five years from diagnosis.
Myeloma occurs when a specific type of cell in the bone marrow is converted into tumour cells. Blood formation is disrupted and patients suffer from a lack of blood resulting in fatigue. The bones can be weakened with a risk of fractures and compacted vertebrae, and patients sometimes suffer kidney failure as a result of the disease.
Antibodies are a part of the immune system, fighting off foreign bodies. Antibody-based drugs are now used to treat certain inflammatory diseases and types of cancer.
The treatment study in Lund will involve 15 patients and is expected to be completed this year. If the results are good, Markus Hansson and his colleagues hope to be able to continue testing BI-505 in larger-scale studies. They will be studying the best way of using the new antibody: alone or in combination with other drugs; at the start of the disease or at a later stage.
Publication:A Human ICAM-1 Antibody Isolated by a Function-First Approach Has Potent Macrophage-Dependent Antimyeloma Activity In Vivo, Cancer Cell, 23(4) pp. 502 - 515
Principal authors: Markus Hansson, Lund University
Niina Veitonmäki and Björn Frendéus, BioInvent
http://www.cell.com/cancer-cell/abstract/S1535-6108(13)00080-9
Contact:Markus Hansson
Phone: +46 705 93 11 10
markus.hansson@med.lu.se
A Human ICAM-1 Antibody Isolated by a Function-First Approach Has Potent Macrophage-Dependent Antimyeloma Activity In Vivo
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Cancer Cell, Volume 23, Issue 4, 502-515, 15 April 2013
Copyright © 2013 Elsevier Inc. All rights reserved.
10.1016/j.ccr.2013.02.026
Authors
Niina Veitonmäki, Markus Hansson, Fenghuang Zhan, Annika Sundberg, Tobias Löfstedt, Anne Ljungars, Zhan-Chun Li, Titti Martinsson-Niskanen, Ming Zeng, Ye Yang, Lena Danielsson, Mathilda Kovacek, Andrea Lundqvist, Linda Mårtensson, Ingrid Teige, Guido Tricot, Björn Frendéussend emailSee Affiliations
Highlights
Function-first screening method rapidly identifies antitumor antibodies
A human anti-ICAM-1 antibody, BI-505, with therapeutic potential
ICAM-1 is highly expressed on the surface of myeloma cells
BI-505 has potent macrophage-dependent antimyeloma activity
Summary
We isolated a tumor B-cell-targeting antibody, BI-505, from a highly diversified human phage-antibody library, using a pioneering “function-first” approach involving screening for (1) specificity for a tumor B cell surface receptor, (2) induction of tumor programmed cell death, and (3) enhanced in vivo antitumor activity compared to currently used treatments. BI-505 bound to intercellular adhesion molecule-1, identifying a previously unrecognized role for this receptor as a therapeutic target in cancer. The BI-505 epitope was strongly expressed on the surface of multiple myeloma cells from both newly diagnosed and relapsed patients. BI-505 had potent macrophage-dependent antimyeloma activity and conferred enhanced survival compared to currently used treatments in advanced experimental models of multiple myeloma.