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Early Results Promising for Autologous HSP Vaccine in Pancreatic Cancer

Early Results Promising for Autologous HSP Vaccine in Pancreatic Cancer

COPENHAGEN, Denmark- Preliminary work with a cancer vaccine derived from heat-shock proteins (HSPs) taken from the patient's own tumor has led to impressive early results in resected pancreatic cancer. Robert G. Maki, MD, presented the findings at the European Cancer Conference (ECCO 12, abstract 48). Cancer vaccines based on autolo- gous heat-shock proteins are of interest because they can carry a diverse array of peptides representing an individual cancer against which a patient can be vaccinated, said Dr. Maki, of the Division of GI Oncology, Department of Medicine, Memorial Sloan- Kettering Cancer Center. "This heat-shock-protein-based cancer vaccine contains the antigenic fingerprint of the patient's particular cancer, and is designed to direct the body's immune system to target and destroy only cancer cells bearing that specific antigenic fingerprint," he said. The phase I study included 10 evaluable patients with resected pancreatic adenocarcinoma given an autologous vaccine (heat-shock protein peptide complex-96). Although the average survival after surgery for pancreatic cancer is 14 to 15 months, patients in this trial had a median survival of 2.5 years, Dr. Maki reported. One patient was still alive and without disease after 5 years, and two other patients were alive and disease-free after more than 2 years following treat- ment. There was no significant observed toxicity associated with the vaccine therapy. The trial enrolled patients who had undergone pancreatic resection and were considered disease-free at vaccination. None had received chemotherapy or radiation therapy. Within 8 weeks of surgery, they began treatment: one vaccination of 5 μg HSPPC- 96 derived from their own tumor each week for 4 weeks. During vaccination, patients were followed by ELISpot assay of autologous T cells against antigen-presenting cells loaded with autologous HSPPC- 96. After the vaccination, patients were followed clinically by CT scan and CA-19-9 every 3 months for 1 year for evidence of recurrence and about every 6 months thereafter. "What is notable is the duration of the survival observed in this study, since more than 90% of patents with pancreatic cancer die within 2 years of diagnosis despite surgical treatment," Dr. Maki said. "Combined with the lack of dose-limiting toxicity observed in this trial, these preliminary results are promising and support the further evaluation of cancer vaccines." Dr. Maki warned, however, that physicians and patients should not get too excited about the results of this initial research as it is too early to tell whether it will be possible to create personalized cancer vaccines for all pancreatic cancer patients, and also because the patients involved in this trial had been carefully selected. "We may be biased in who we selected for this study. Only patients who could have an operation were eligible. Furthermore, we screened out those who had evidence of tumor spread before they entered the study. Perhaps, just by chance, we got a few people who were destined to do well," Dr. Maki said. "We need a proper randomized study to determine the vaccine's usefulness." He pointed out that there were initial problems with the vaccine's manufacturing process, and the study was delayed half way through to improve the vaccine-making process. "The problem is that the pancreas makes specific digestive enzymes that destroy proteins," Dr. Maki said. "In other words, the pancreatic tumor cells themselves can destroy the vaccines you are trying to make if you do not handle the tumor tissue carefully and quickly." With improvements in the vaccine-purification process, he said, most patients enrolled in the study were able to receive the vaccine. Other Cancers
The results from the phase I pancreatic cancer trial are "consistent with what we have observed in trials of this vaccine with other cancers," Dr. Maki said. The vaccine is being tested in phase III trials in renal cell carcinoma and metastatic melanoma, and is also being studied in gastric cancer, non- Hodgkin's lymphoma, and colorectal cancer. New York-based Antigenics Inc., the company sponsoring these trials, has been granted fast track and orphan drug designations from the FDA for HSPPC-96 (Oncophage) in both metastatic melanoma and renal cell carcinoma.

 
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