Today, Cell Genesys (Foster City, CA USA) announced preliminary data from their Phase II trial of GVAX(R) vaccine for resectable pancreatic cancer. The non-patient specific whole cell vaccine showed marked efficacy compared to standard of care. In 60 patients with operable pancreatic cancer, who received the vaccine after surgical resection and adjuvant therapy, the one year survival was 88% and the two year survival was 76%. Historical data gives a mean survival for similar patient epidemiology in the range of 40-50%. Even more impressively, 52 of these patients were classed as stage IIb; having metastases present in the lymph nodes.
The GVAX platform is an elegant idea. The vaccine consists of tumor cells that have been modified through either plasmid transfection, adenoviral or even retroviral transduction to overexpress granulocyte-macrophage colony stimulating factor (GM-CSF), a potent immunostimulator. The cells are then irradiated to stop proliferation, and reintroduced to the patient transdermally. Irradiated GM-CSF-secreting whole cell vaccines induce antitumor responses through the recruitment of antigen-presenting cells. The most potent of these, dendritic cells, in turn activate specific CD4+ and CD8+ T cells through tumor cell peptide presentation. Previous work, by Hung and colleagues, has shown that CD4+ T cells thus activated do not merely facilitate CD8+ mediated tumor cell destruction, but simultaneously elicit Th1 and Th2 CD4+ T cell responses. The tumor killing capacity is then a function of more than one mechanism.
Initially, Cell Genesys harvested autologous tumor cells and modified them ex vivo for patient-specific therapy. But more recently and in particular with the pancreatic Phase II trial, the vaccine is a non-patient specific ‘off-the-shelf’ therapy. In this case Cell Genesys have taken the human chronic myeloid leukemia-derived cell line, K562 and formed a stable GM-CSF secreting line that does away with the requirement for autologous cell preparation.
Pancreatic cancer is notoriously hard to treat because symptoms are non-specific and it is rarely caught at an early stage. Current standard of care for this disease is surgery with adjuvant 5-fluorouracil and radiation. Statistics from the American Cancer Society cite that 32,180 Americans (16,100 men and 16,080 women) will be diagnosed with cancer of the pancreas during 2005. Only about 23% of patients with cancer of the exocrine pancreas will be alive 1 year after their diagnosis; only about 4% will live 5 years after diagnosis. Even for those people diagnosed with local disease (has not spread to other organs), the 5-year relative survival rate is only 15%.
The exciting results from the GVAX Phase II trial will be presented by Daniel Laheru, M.D. on November 17th at the AACR-NCI-EORTC International Conference on Molecular targets and Cancer therapeutics being held in Philadelphia, PA, USA.
Message posted by: Simon Chandler
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