According to results recently presented at the 2003 annual European Cancer Conference (ECCO 12) and issued in a press release by the Federation of European Cancer Societies, the heat-shock vaccine Oncophage® may improve survival in patients with operable pancreatic cancer.
The pancreas is an organ that is surrounded by the stomach, small intestine, bile ducts (tubes that connect the liver to the small intestine), gallbladder, liver and spleen. The pancreas helps the body to break down food and produces hormones, such as insulin, to regulate the body’s storage and use of food. For patients whose disease has not spread to distant sites in the body, surgical removal of the cancer typically results in optimal long-term outcomes; however, long-term survival or a cure are rarely achieved for patients with pancreatic cancer. Due to the poor outcomes associated with current treatment for patients with pancreatic cancer, recent research efforts have been focused on evaluating new therapeutic approaches alone or in combination with other treatment modalities in order to improve survival for patients with this disease.
One type of therapy being evaluated extensively for the treatment of cancer is the utilization of the patient's’ own immune system to attack the cancer. Oncophage® (HSPPC-96) is a vaccine that is composed of components of the patient’s own cancer cells and stimulates the patient’s immune system to attack the cancer. Every cell in the body displays specific antigens (small carbohydrates and/or proteins) on their surface. The immune system relies on differences in antigens to distinguish between healthy cells and non-healthy cells or “foreign” material, such as bacteria, viruses or cancer cells. Dendritic cells are specific immune cells that “present” or display antigens of non-healthy cells or foreign material to other cells in the immune system. The immune system then mounts an attack against the unwanted cells displaying the antigen(s) that were presented by the dendritic cells.
Heat shock proteins (HSPs) are proteins that exist in every cell in the body and their many roles are becoming more apparent to researchers. One important role of HSPs is to form a complex with antigens from a cell that is considered not healthy, such as a cancer cell. HSPs of a cancer cell form a complex with antigens specific to the cancer cell. Clinical studies have revealed that when HSPs from a cancer cell loaded with antigens bind to a dendritic cell, the HSP/antigen complex is internalized and biochemical processes occur within the dendritic cell that stimulate the immune system to attack the cancer. First, this process allows the dendritic cell to “display” the antigens specific to the cancer cells to other immune cells to initiate an immune response against the cancer. In addition, this process has been shown to induce dendritic cells to secrete cytokines, substances released into the lymph that stimulates immune cells, and to induce dendritic cell maturation.
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Oncophage® is prepared by isolating HSPs/antigen complexes from a patient’s cancer cells obtained from the surgical removal of cancerous tissue. The HSP/antigen complexes are made into a vaccination to stimulate the patient’s immune system against cancer cells throughout the body. Patients typically receive Oncophage® once a week on an outpatient basis. Oncophage® has demonstrated encouraging results in various cancers and is in early clinical trials for the treatment of pancreatic cancer.
Researchers recently conducted a small clinical trial to evaluate Oncophage® in the treatment of pancreatic cancer. This trial included 10 patients with pancreatic cancer that had not spread to distant sites in the body. Each patient underwent surgery to remove part of the pancreas, and within 8 weeks of surgery was treated with Oncophage®. The average overall survival for these patients was 2.5 years, which compares favorably to the usual average duration of survival for these patients, 16 months. One patient is alive and cancer free for more than 5 years following therapy, and 2 other patients are alive and cancer-free at 2.5 and 2.2 years following therapy. Treatment with Oncophage® in this trial consisted of one vaccination per week for a duration of 4 weeks. There were no side effects associated with Oncophage®.
These researchers concluded that the addition of Oncophage® to surgery may improve survival in patients with pancreatic cancer. Future clinical trials directly comparing patients who undergo surgery with or without Oncophage® will help to determine the true clinical benefit of this vaccine. Although the FDA has suspended late clinical trials evaluating Oncophage® in melanoma and kidney cancer due to the need for more information, earlier-stage clinical trials, such as those evaluating Oncophage® for pancreatic cancer, are not affected by this ruling. Patients with operable pancreatic cancer may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating Oncophage® or other promising therapeutic approaches.
Reference: Antigenics Inc. Data from Phase I trial of Oncophage vaccine in pancreatic cancer highlighted at European Cancer Conference (ECCO 12). Overall survival of 2.5 years reported in pancreatic cancer patients receiving Oncophage. Available at: http://www.antigenics.com/news/2003/0922.phtml. Accessed September 22, 2003.