Genzyme Molecular Oncology Investigators See Immune Response in Melanoma Cancer Vaccine Phase I/II Trial
FRAMINGHAM, Mass., May 22 /PRNewswire/ -- Genzyme Molecular Oncology (Nasdaq: GZMO - news) announced today that investigators of its phase I/II melanoma cancer vaccine trial have observed immune responses in several patients. Of nine patients enrolled to date, two have been evaluated for immune response and both have shown laboratory evidence of immunity. Additionally, three of the nine patients have developed vitiligo-another indication of immune response. Preliminary data also shows that the vaccine is feasible and well-tolerated.
These and additional observations from the trial were presented by lead investigator Frank Haluska, M.D., Ph.D. of the Massachusetts General Hospital Cancer Center, Boston, at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO) in New Orleans.
The phase I/II trial is assessing the safety, efficacy, and potency of a cancer vaccine for melanoma, the most serious type of skin cancer. The vaccine utilizes dendritic cells and combines two of the most widely expressed melanoma tumor antigens, Melan-A/MART-1 and gp100 in a gene-based vaccine. The antigens function like neon signs that alert T-cells (cells that destroy tumors), to find and attack the melanoma cells.
"The exciting observations of immune response in this molecularly targeted therapy, though preliminary, are very encouraging," said Haluska. "By engaging the immune system's innate ability to find and destroy cancer cells, a successful gene therapy cancer vaccine for melanoma would offer patients a less invasive alternative to current treatments like chemotherapy, with few, if any, side effects. To date, we have observed no significant adverse effects related to vaccination."
Dr. Haluska presented results of several immunologic tests that revealed evidence of immune responses in four patients, including the appearance of vitiligo in three of the patients treated. Vitiligo has been observed in these patients at the lowest dose level.
Vitiligo is a skin condition in which various tissues lose pigmentation due to the immune destruction of melanocytes, or cells that produce pigment. Onset of the disorder suggests that an immune response, elicited by the melanoma antigens in the vaccine, is being generated against melanocytes. This is the first dendritic cell vaccine trial in which vitiligo has been observed. However, it has been occasionally observed in response to other types of melanoma vaccines, and in those cases was correlated with clinical response.
Two other immunologic tests also showed evidence of an immune response in some patients. In visual and histologic tests for Delayed Type Hypersensitivity (DTH) response-a skin test that assesses T-cell reactions against the antigens presented-two patients showed evidence that T-cells had formed and reacted against the Melan-A/MART-1 and gp100 antigens. Additionally, Dr. Haluska reported that two patients showed evidence of the formation of antigen specific cytotoxic T-lymphocytes, T-cells that kill tumor cells.
Mark Goldberg, senior vice president, Medical Affairs, Genzyme, commented, "Our goal has been to design the melanoma trial to maximize the immune response against the cancer. This design is expected to provide us with data that enable us to optimize cancer vaccine trials for a range of other cancers. Genzyme Molecular Oncology is also moving forward in its antigen discovery program and we expect to file an IND in the first half of next year for our first proprietary antigen for use in a cancer vaccine."
The trial began in April 1999 and will enroll up to 24 stage III or IV melanoma patients. Enrollment is expected to be complete by the end of this year. People suffering from metastatic melanoma are encouraged to call and inquire about entry requirements for the trial at 617-724-7081.
Background On Melanoma Trial
Genzyme Molecular Oncology's phase I/II melanoma trial is being conducted through the Dana-Farber Partners Cancer Care, which includes Massachusetts General Hospital, Brigham and Women's Hospital, and the Dana-Farber Cancer Institute.
This trial has incorporated several elements that distinguish it as leading edge. The trial is evaluating the combination of two tumor antigens to increase the potency of the vaccine and is capitalizing on the immune stimulating abilities of dendritic cells to elicit a powerful immune response.
The vaccine is gene-based, in contrast to the protein or peptide vaccines used in many other tumor vaccine trials, providing more prolonged presentation of the antigens to T-cells. This increased stimulation enhances the ability of the T-cells to attack tumor cells.
Additionally, some patients in the trial are receiving low dose IL-2, a general immune response stimulant, to boost the immune response. A recent peer reviewed publication reported a dramatic effect in preclinical studies when low dose IL-2 was combined with a dendritic cell-based vaccine.
Genzyme Molecular Oncology has completed two phase I cancer vaccine trials in melanoma. These studies demonstrated that treatment with either the Melan-A/Mart-1 or the gp100 antigen was safe and well-tolerated. In addition, a number of patients showed significant tumor regression.
The American Cancer Society estimates that approximately 47,700 people in the U.S. will be diagnosed this year with melanoma and that approximately 7,700 people in the U.S. will die from melanoma this year. In addition, less than five percent of patients with metastatic melanoma will live five years or more. The lifetime incidence of melanoma has increased from one in 500 to one in 105 since 1935.
Melanoma is characterized by four stages, with Stage IV being the most severe. Currently, Stage IV patients are treated with chemotherapy which may result in tumor shrinkage but rarely improves long term patient survival. These patients may also be treated with recombinant high dose IL-2, the first therapy approved by the FDA for the treatment of metastatic melanoma in over 20 years. High dose IL-2 is associated with high toxicity and has an overall response rate of approximately 17 percent.
Genzyme Molecular Oncology is developing a new generation of cancer products focusing on cancer vaccines and angiogenesis inhibitors. It is shaping these new therapies through the integration of its genomics, gene and cell therapy, small-molecule drug discovery, and protein therapeutic capabilities.
A division of Genzyme Corporation, Genzyme Molecular Oncology has its own common stock intended to reflect its economic value and track its performance.
This press release contains forward-looking statements, including statements concerning preliminary data concerning the feasibility and safety of the vaccine, the anticipated benefits of a gene therapy cancer vaccine, the expected significance of the onset of vitiligo in trial patients, the anticipated benefits arising from the trial design, the planned timing of a regulatory submission and completion of trial enrollment, and estimates concerning the melanoma patient population and response rates to high dose IL- 2. Actual results may materially differ due to numerous factors, including the timing and results of the final analysis of trial data, the actual safety and efficacy of the vaccine, the ability to identify and enroll additional stage III and IV melanoma patients in the trial and the actual timing of enrollments, decisions made by regulatory authorities, the accuracy of information obtained by Genzyme Molecular Oncology on the melanoma patient population, market acceptance of cancer vaccines, and the risks and uncertainties described in Genzyme's filings with the Securities and Exchange Commission under the Exchange Act of 1934, as amended, including Exhibit 99.2 to Genzyme's Annual Report on Form 10-K for the year ended December 31, 1999.
Genzyme's releases are on the World Wide Web at genzyme.com. They are also available from Genzyme's fax-on-demand service at 1-800-436-1443 within the United States or 1-201-521-1080 outside the United States.
SOURCE: Genzyme Molecular Oncology |
