A human cancer vaccine has, for the first time, been observed to promote the invasion of cancerous tissues by specific families of white blood cells that are believed to have a cancer-fighting effect.
In a presentation last year, David Berd, MD, of Thomas Jefferson University's division of neoplastic diseases, explained how administration of a special vaccine to patients who had undergone surgery for malignant melanoma that had spread to lymph nodes had greatly increased the percentage of 5-year survivors. The next question was, "Why?"
Now the same Jefferson research team, along with researchers led by Giorgio Parmiani, MD, and Marialuisa Sensi, PhD, of the Instituto Nazionale Tumori in Milan, Italy, believe that they have an explanation. For the first time, the researchers demonstrated that a human cancer vaccine promotes the invasion of cancer tissue by specific families of white blood cells.
Results of Six-Patient Study Reported
In a new paper appearing in the Journal of Clinical Investigation, the investigators report the results of a study of six patients with malignant melanoma. The patients were treated with a vaccine containing their own cancer cells coated with the chemical dinitrophenyl (DNP). The DNP appears to make cancer cells appear more foreign to the patients' immune systems, so that it can mount a fight against the tumor.
"In our previous studies, we found that the DNP vaccine causes the development of inflammation in the tumors." explained Dr. Berd. "In other words, they become red and swollen and microscopic examination shows that they are invaded by a particular type of white blood cell, called a T cell. In this study, Dr. Parmiani's laboratory showed that these were not just any old T cells, but particular clones of T cells that had been elicited by the vaccine. To my knowledge, this has never before been demonstrated for a human cancer vaccine."
The investigators used the tools of molecular biology--polymerase chain reaction (PCR) and cloning of fragments of DNA--to identify the structures of the T-cell receptors of the white blood cells invading the tumors. If certain chemical constituents or antigens on the melanoma cells had elicited the T-cells, it would have been expected that the T-cells with certain receptor structures would be detected in large quantities within the tumors. That is precisely what the research team found.
In the tumors of five patients in this study, a special family of T-cells was much more abundant after treatment with the vaccine than before the treatment. Even more surprising was the observation that vaccine-treated tumors were invaded by clones of T-cells that were not detectable in tumors before vaccination, nor in T-cells circulating in the blood stream.
Dr. Berd believes that the new molecular biology study provides a scientific explanation for the therapeutic results. These findings may be a key to developing a more effective immunotherapy against malignant melanoma, the deadliest from of skin cancer. In recent years, mortality from melanoma has been increasing. In 1995, the National Cancer Institute (NCI) expected more than 34,000 new individual cases of melanoma in the United States alone, and almost 7,200 individuals died from the disease. The incidence has increased nearly 80% between 1973 and 1987, at a rate of approximately 4% per year (NCI CancerNet).
Vaccine Being Used to Treat Advanced, But Resectable Melanomas
The vaccine under investigation is being used postsurgically for treating advanced, but surgically resectable, malignant melanoma. According to Dr. Berd's 1996 interim results, patients with stage III tumors in the lymph nodes were treated with the vaccine after standard lymphadenectomy. Of 62 patients who received the vaccine, 47% had not relapsed after 5 years, and 58% survived for 5 years. This compared to the 20% to 25% survival rate in patients treated with surgery alone. The patients also received a low dose of cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar), a medication commonly used in cancer chemotherapy, but which has been shown to boost the immune system when administered in the right way.
In a joint agreement with Thomas Jefferson University and Dr. Berd, AVAX Technologies, Inc, a development-stage biotech company headquartered in Kansas City, has acquired the exclusive nights to develop and commercialize the patented DNP-vaccine technology under the trade name AC MelaVax. Beginning first with melanoma, the company believes that the same technology could be adapted to the treatment of other cancers.
"In the past," noted Dr. Berd, "the field of cancer vaccines has overpromised and underperformed. But in view of the progress we've made, I'm eagerly looking forward to the additional required testing that could confirm our very encouraging results." Concluded Dr. Berd, "The research itself is exciting, but providing a new treatment for cancer--that would be most gratifying."
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