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," he stressed.