Cambridge Antibody Technology and Human Genome Sciences Inc. announced that HGSI has exercised an option to enter into an exclusive development partnership on a human monoclonal antibody to Trail Receptor-2 (Trail-R2 mAb). Trail-R2 mAb is an agonistic antibody that specifically recognises the Trail Receptor-2 protein, found on the surface of a number of cancer cell types.
In pre-clinical studies, Trail-R2 mAb has demonstrated the ability to reduce or prevent the growth of certain tumours in animal models.
HGSI discovered Trail Receptor-2. Trail Receptor-2 is a member of the tumour necrosis factor (c) family of receptors, and is called a "death receptor" because of its ability to cause tumour cell death when triggered by the natural ligand Trail (tumour necrosis factor-related apoptosis-inducing ligand). Trail Receptor-2 has been shown to be expressed on a number of solid tumours, including lung, prostate and breast tumours, and tumours of hematopoietic origin. It has been demonstrated that cell lines derived from such tumours are sensitive to killing by apoptosis induced by binding to Trail and Trail-R2 mAb.
Unlike the natural Trail ligand, Trail-R2 mAb does not bind to the surface proteins DcR1 and DcR2 or the soluble receptor osteoprotegerin. Trail binds to these proteins, but such binding does not trigger cell death.
HGSI and CAT announced an antibody product development alliance in early 2000. The agreement provides HGSI with rights to use CAT's antibody technology to develop and sell human antibodies for therapeutic and diagnostic purposes. In return, CAT is entitled to receive licence fees, clinical development milestones and royalties on product sales from HGSI.
Trail-R2 mAb is the third HSGI antibody drug candidate to emerge from the collaboration between HGSI and CAT. The others are Trail-R1 mAb, a human monoclonal antibody to Trail Receptor-1 for use in treating certain cancers, and LymphoStat-B, a human monoclonal antibody to BLyS (B-lymphocyte stimulator) for use in treating lupus and rheumatoid arthritis. HGSI holds the commercial rights to all three drugs. These drugs will be produced in the HGSI manufacturing facility located in Rockville, Maryland, USA.Peter Chambré, CAT's CEO, said, "We are delighted that our collaboration with Human Genome Sciences continues to progress rapidly. We are proud to follow the achievements on the Trail-R1 human antibody with the successful isolation of the Trail-R2 human antibody.
Significantly, Trail-R2 mAb, like Trail-R1 mAb, is directed to a cell-surface receptor protein. We look forward to further success in our collaboration with HGSI."
William A. Haseltine PhD, Chairman and Chief Executive Officer of Human Genome Sciences, said, "Our collaboration with Cambridge Antibody Technology is clearly productive. In November 2001, we announced clearance by the US Food and Drug Administration to initiate human testing of LymphoStat-B for use in treating lupus and rheumatoid arthritis. At the end of April 2002, we announced clearance to initiate human testing of Trail-R1 mAb for use in treating solid tumours and tumours of hematopoietic origin. Trail-R1 mAb is specific to Trail Receptor-1, while Trail-R2 mAb is specific to Trail Receptor-2. The activity of both molecules is novel. Both are designed to mimic the activity of the natural Trail ligand, which stimulates these receptors to cause cancer cell death through apoptosis. Both also are designed to have the advantage of a longer half-life and the potential for greater efficacy than Trail itself. We look forward to completing the pre-clinical development of Trail-R2 mAb, and to entering this promising anti-tumour drug candidate into clinical trials."