Colella tests how to boost the body's immune response to melanoma

By Anne Bromley

Stephanie Gross

Teresa Colella found that the immune response to melanoma is stronger when an enzyme called tyrosinase, which is involved in skin color, is removed. As a result, the research team is modifying the vaccine's peptide chain containing tyrosinase.

The body's immune response gets triggered when the system recognizes something as foreign. Conversely, the immune system does not attack normal tissue: T-cells, the body's warrior cells, are taught, or "tolerized" to ignore proteins of normal cells.

Researchers at U.Va., led by immunologist Victor Engelhard, tumor oncologist Craig Slingluff and chemistry professor Donald Hunt, have reached the clinical trial stage in testing a vaccine against skin cancer. Teresa-Anne Colella, in her sixth and final year in Engelhard's laboratory in the microbiology department, is working on ways to improve the vaccine, thereby boosting the immune response. She recently won first prize at the Graduate Research Exhibition in the category, "Biological and Biomedical Sciences," for a presentation of her work.

The interdisciplinary team pursued the vaccine possibility "because it turns out that some melanoma patients undergo spontaneous regression of their tumors, and others respond to immunotherapeutic intervention, suggesting that their immune systems recognized and killed their cancer cells," Colella explained in her recent talk. "In addition, melanoma patients' cancer cells and immune cells can be grown in culture in the lab, making them easy to study," she said.

The vaccine is made from peptide antigens on cancer cells. The problem is that the peptides are derived from proteins expressed in normal skin cells. Using mice, whose immune systems have been humanized, Colella is trying to figure out if the T-cells can distinguish the peptide antigens on melanoma cells as foreign even though the proteins from which they are derived are normally expressed in the skin. She has discovered that the enzyme tyrosinase, essential for normal skin pigmentation, limits the immune response to the tyrosinase-derived melanoma antigen. Colella and her colleagues have found that when they remove tyrosinase from mice, the immune system responds much better to fighting the melanoma cells. They are now trying to decipher how tolerance to tyrosinase is maintained, and they are testing slightly modified versions of the tyrosinase peptide vaccine in mice that express tyrosinase to see if the immune system's tolerance can be overcome, so that the T-cells can be activated to destroy the melanoma cells.

"Research can be frustrating, but it is also exciting. All I have to do is walk by the Cancer Center and see the patients in the reception area, and I am reminded that all of the hard work is worthwhile," said Colella, who is currently interviewing for post-doctoral positions. She hopes to combine her interests in vaccine research and public health.