PARIS, France--Cancer vaccines are now coming into their own,
in advanced as well as early disease, Malcolm S. Mitchell, MD,
said at the Fifth International Congress on Anti-Cancer Chemotherapy.
Although vaccines have, to date, been most extensively investigated
in melanoma, the adenocarcinomas will soon be treated by this
approach as well, said Dr. Mitchell, of the University of California
at San Diego.
The most exciting prospect, he believes, is the MUC-1 peptide
breast cancer vaccine, which will be started in clinical trials
within the next few months. This vaccine is based on antigens
to the mucin core protein, which breast cancer shares in common
with gastrointestinal, ovarian, and lung cancer.
Another extremely fertile area for vaccine development, he predicted,
is in such chemotherapy-resistant squamous cell carcinomas as
lung cancer and head and neck cancer.
In Los Angeles and now in La Jolla, Dr. Mitchell's team has used
vaccines to treat 154 patients with metastatic melanoma in the
last 10 years. Although, at first glance, the 20% response rate
may appear discouraging, he said, some 10% of patients do survive
for at least 3 to 8 years with monthly maintenance vaccine injections.
"Tumor-induced immunosuppression is a reality," Dr.
Mitchell said, noting that transforming growth factor-beta (TGF-beta),
interleukin-10, and GM-CSF are all immunosuppressive molecules
secreted by tumor cells. To avoid this tumor-related immunosuppression,
he urged that active immunotherapy be started at the earliest
stages of disease, when the tumor burden is small.
The optimal tumor antigens, Dr. Mitchell said, are those that
maximize the responses of both cytotoxic and helper T cells. "CD4+
helper cells may actually control the major mechanisms by which
tumor cells are rejected in vivo, through the cytokines they produce
and the other leukocytes they evoke," he said.
Also desirable for subunit vaccines, he pointed out, is that the
antigens be defined by human T cells rather than by mouse monoclonal
antibodies. "It's more important to know what a human sees
as being an antigen than what a mouse sees on a human cell,"