Genmab’s Hand-me-down
By Christopher Maggos
Senior Writer, BioCentury
In 2005, Genmab A/S plucked a bundle of cancer targets from the remains of former proteomics company Europroteome AG. Last month, Genmab provided its first look into the assets, announcing it is developing antibodies against a new target, ZP3A, a protein that is highly over-expressed in multiple solid tumors but not in normal tissue. The antibodies work via ADCC and complement activation, and the company hopes they’ll reach
the clinic by 2008.
Zona pellucida glycoprotein 3A (ZP3A) is found on the surface of oocytes, where it helps sperm bind to the egg. It also is present at low levels in healthy human colon, but not in critical organs like the brain, heart, liver or lungs.
Genmab (CSE:GEN, Copenhagen, Denmark) obtained the rights to ZP3A and 15 other undisclosed targets from Europroteome’s insolvency process for an undisclosed amount, and does not owe milestones or royalties on products that result (see BioCentury, May 23, 2005).
“ZP3 is the first Europroteome target that we’ve talked about publicly,” EVP and CSO Jan van de Winkel told BioCentury. The effects of targeting ZP3A are poorly understood. “It plays a role in signaling and has something to do with calcium mobilization and G protein activation,” van de Winkel said. Rather than trying to block ZP3A’s activities, GEN’s strategy is to use the protein as a flag marking cells for destruction. GEN discovered several antibody candidates that bind various ZP3A epitopes and that kill cells expressing ZP3A via both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
In a xenograft mouse model of colon cancer, where tumors were carrying both ZP3A and HER2, GEN’s HuMab-012 stopped tumor growth as effectively as Herceptin trastuzumab and reduced tumor size more effectively than Herceptin, the anti- HER2 antibody from Genentech Inc. (DNA, South San Francisco, Calif.).
GEN chose to test its ZP3A antibodies in colon cancer before other indications for purely practical reasons. “Different animal models for colon cancer were already fully operational within Genmab,” van de Winkel said. Other animal models, including one for pancreatic cancer, are being prepared. The company has not decided which indication it will pursue first, he said. |
