Human Genome Sciences Presentations at the American Association for Cancer Research 93rd Annual Meeting
Antitumor Activity of TRAIL Receptor-1 Agonistic Human Monoclonal Antibody
ROCKVILLE, Md., April 10 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI - news) described today data presented at the American Association for Cancer Research meeting held in San Francisco from April 6-10, 2002. Company scientists presented posters regarding several novel compounds for cancer treatment.
TRAIL Receptor-1 Human Monoclonal Antibody
Human Genome Sciences is currently developing TRAIL Receptor-1 monoclonal antibody (TRAIL-R1 mAb; referred to as TRM-1 in conference abstracts) as a potential new drug for the treatment of solid tumors. The drug is a human monoclonal antibody that recognizes TRAIL Receptor-1, which is over-expressed on the surface of many tumors including colon, breast, lung and other carcinomas and cell lines from these tumors.(1) The TRAIL receptor is an especially interesting target for antibody drugs, as binding of the natural protein, TRAIL (tumor necrosis factor-related apoptosis inducing ligand), to TRAIL Receptor-1 triggers apoptotic cell death.(2) TRAIL Receptor-1 is a member of the tumor necrosis factor receptor family.(3) The Human Genome Sciences antibody mimics the activity of natural TRAIL. As such, it is considered an agonistic antibody. Binding of the antibody to the receptor triggers the death of some tumor cells.(4)
An abstract presented on April 8, entitled Generation of Human Therapeutic Anti-TRAIL-R1 Agonistic Antibodies by Phage Display, describes the isolation and characterization of the TRAIL-R1 antibody drug candidate. More than one hundred antibody candidates were made and assessed for antitumor activity using a human cancer cell line. The antibody selected as the lead candidate was shown to be highly potent in its activity against cervical carcinoma cells in culture. Generation of the antibody candidate and further characterization were performed jointly by a team of scientists from Cambridge Antibody Technology and Human Genome Sciences. (Abstract #2869)
A second abstract, Antitumor Activity of TRAIL-R1 mAb, a fully human therapeutic TRAIL-R1 agonistic mAb, was presented on April 9 and summarizes experiments that demonstrate TRAIL-R1 monoclonal antibody's potent antitumor activity in both in vitro cell culture and in vivo animal models. TRAIL-R1 mAb inhibited the tumor formation of a human colon carcinoma and the growth of pre-established uterine tumors in athymic mice. The study also shows that the antitumor activity of TRAIL-R1 mAb works in conjunction with chemotherapeutic agents, such as topotecan or irinotecan to achieve even greater antitumor effect. In addition, the TRAIL-R1 mAb induced no significant hepatocyte cell death in an in vitro cell culture system. (Abstract #4240)
Summary
The results of these studies suggest that TRAIL Receptor-1 human agonistic monoclonal antibody is an attractive candidate for the treatment of solid tumors... |
