One of their most significant discoveries is that the mEGP antigen inhibits tumor cell invasion in vitro and metastases in vivo. The same in vitro effects are seen in humans with the GA733 antigen.
Colorectal cancer cells (CRC) produce an abundance of the GA733 antigen. By designing an antibody that recognizes and attacks the antigen, Dr. Herlyn's research team has successfully increased the survival rate of CRC patients in a randomized clinical trial. Despite the success of the antibody, however, little has been known about the function of the GA733 antigen. Not only does it sit on the surfaces of ovarian, lung and most epithelial tumors, but it also is expressed by normal tissues.
"It is ironic," says Dr. Herlyn, "that immunotherapy works against an antigen that controls metastases and kills tumor cells. Obviously, connecting the therapy success with the function of the antigen is the difficult part."
According to Dr. Herlyn, "the GA733 antigen is the glue that makes tumor cells stick together and form clumps, which may be how invasion is inhibited. In fact, that may be its most important function," she explains.
An antigen is defined as any agent that elicits an immune system response.
Under normal conditions, antigens stimulate the production of specific
lymphocytes or antibodies that may in turn destroy the cells bearing the
antigens. In patients with colorectal cancer (CRC), however, the antigens
expressed by their growing tumors do not generally cause sufficient immune
Contact: Diana Cutshall
The Wistar Institute