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 system responses to prevent the growth and spread of the tumor cells.
Studies of the GA733 antigen are part of a $6.6 million program project funded by the National Cancer Institute, for which Dr. Herlyn is the principal investigator. The primary goal of the project is to evaluate the humoral and cellular immune responses of CRC patients to vaccination with the GA733 antigen.
The program project will conclude with a Phase I clinical trial that will give insight into the immunological mechanisms that might underlie the possible clinical effects of the vaccine. Both humoral and cellular immune responses have been shown to play important roles in the control of tumor growth.
The Wistar Institute, established in 1892, was the first independent medical research facility in the country. For more than 100 years, Wistar scientists have been making history and improving world health through their development of vaccines for diseases that include rabies, German measles, infantile gastroenteritis (rotavirus), and cytomegalovirus; discovery of molecules like interleukin-12, which are helping the immune system fight bacteria, parasites, viruses and cancer; and location of genes that contribute to the development of diseases like breast, lung and prostate cancer. Wistar is a National Cancer Institute Cancer Center.
Journal
JNCI Journal of the National Cancer Institute