Colella tests how to boost the body's
immune response to melanoma
By Anne Bromley
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.
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.
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.
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,"
people in the U.S. have had or are afflicted with melanoma,
or skin cancer.
is the seventh most common type of cancer in this country,
the most prevalent cancer among women age 25 to 29.
death rate from melanoma has tripled in the past four decades.
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.
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