Study Offers Scientific Explanation For Effectiveness of Melanoma Vaccine

A human cancer vaccine has, for the first time, been observed to promotethe invasion of cancerous tissues by specific families of white blood cellsthat are believed to have a cancer-fighting effect.

In a presentation last year, David Berd, MD, of Thomas Jefferson University'sdivision of neoplastic diseases, explained how administration of a specialvaccine to patients who had undergone surgery for malignant melanoma thathad spread to lymph nodes had greatly increased the percentage of 5-yearsurvivors. The next question was, "Why?"

Now the same Jefferson research team, along with researchers led byGiorgio Parmiani, MD, and Marialuisa Sensi, PhD, of the Instituto NazionaleTumori in Milan, Italy, believe that they have an explanation. For thefirst time, the researchers demonstrated that a human cancer vaccine promotesthe 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 malignantmelanoma. The patients were treated with a vaccine containing their owncancer cells coated with the chemical dinitrophenyl (DNP). The DNP appearsto 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 causesthe development of inflammation in the tumors." explained Dr. Berd."In other words, they become red and swollen and microscopic examinationshows that they are invaded by a particular type of white blood cell, calleda T cell. In this study, Dr. Parmiani's laboratory showed that these werenot just any old T cells, but particular clones of T cells that had beenelicited by the vaccine. To my knowledge, this has never before been demonstratedfor a human cancer vaccine."

The investigators used the tools of molecular biology--polymerase chainreaction (PCR) and cloning of fragments of DNA--to identify the structuresof the T-cell receptors of the white blood cells invading the tumors. Ifcertain chemical constituents or antigens on the melanoma cells had elicitedthe T-cells, it would have been expected that the T-cells with certainreceptor 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-cellswas much more abundant after treatment with the vaccine than before thetreatment. Even more surprising was the observation that vaccine-treatedtumors were invaded by clones of T-cells that were not detectable in tumorsbefore vaccination, nor in T-cells circulating in the blood stream.

Dr. Berd believes that the new molecular biology study provides a scientificexplanation for the therapeutic results. These findings may be a key todeveloping a more effective immunotherapy against malignant melanoma, thedeadliest from of skin cancer. In recent years, mortality from melanomahas been increasing. In 1995, the National Cancer Institute (NCI) expectedmore than 34,000 new individual cases of melanoma in the United Statesalone, and almost 7,200 individuals died from the disease. The incidencehas increased nearly 80% between 1973 and 1987, at a rate of approximately4% per year (NCI CancerNet).

Vaccine Being Used to Treat Advanced, But Resectable Melanomas

The vaccine under investigation is being used postsurgically for treatingadvanced, but surgically resectable, malignant melanoma. According to Dr.Berd's 1996 interim results, patients with stage III tumors in the lymphnodes were treated with the vaccine after standard lymphadenectomy. Of62 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% survivalrate in patients treated with surgery alone. The patients also receiveda low dose of cyclophosphamide (Cytoxan, Neosar), a medication commonlyused in cancer chemotherapy, but which has been shown to boost the immunesystem 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 headquarteredin Kansas City, has acquired the exclusive nights to develop and commercializethe patented DNP-vaccine technology under the trade name AC MelaVax. Beginningfirst with melanoma, the company believes that the same technology couldbe adapted to the treatment of other cancers.

"In the past," noted Dr. Berd, "the field of cancer vaccineshas overpromised and underperformed. But in view of the progress we'vemade, I'm eagerly looking forward to the additional required testing thatcould confirm our very encouraging results." Concluded Dr. Berd, "Theresearch itself is exciting, but providing a new treatment for cancer--thatwould be most gratifying."