Most attempts to create therapeutic cancer vaccines are based on custom-made approaches that use a patient's own tumor cells to generate a strong immune response against cancer. However, developing these kinds of personalized vaccines is time-consuming, expensive and often impractical. Using an alternative approach, researchers at the University of Pittsburgh Cancer Institute (UPCI) in collaboration with the Gunma University School of Medicine in Japan, have developed a vaccine strategy for head and neck cancer that targets multiple peptides (parts of proteins) to activate the immune system to attack tumors.
The researchers created the vaccine to target a tumor suppressor gene called p53, which is mutated in most cancers and associated with poor clinical outcomes. Previous research has determined that mutated p53 also expresses unaltered, or "wild-type," p53 peptides in tumors. When presented on dendritic cells, these wild-type p53 peptides may induce an immune response to strengthen the body's natural defenses against cancer and decrease the chance of cancer recurrence and the formation of secondary tumors.
"The key to our strategy is to select those p53 peptides that can best activate the immune system and induce it to produce immune cells able to recognize and eliminate the tumor," said Theresa Whiteside, Ph.D., who in collaboration with Albert DeLeo, Ph.D., directed the study. Both investigators are professors of pathology and immunology at the University of Pittsburgh School of Medicine. "Through animal models and human cells in culture, we have found that this strategy is very effective at stimulating T cells into action," said Dr. Whiteside, who also directs UPCI's Immunologic Monitoring and Cellular Products Laboratory. According to Dr. DeLeo, the vaccine based on these findings also could be relevant to other types of cancer given that the loss of p53 function is a common feature across many cancers.
The vaccine is based on three peptides derived from p53 that target killer T cells and helper T cells. Although killer T cells directly destroy tumor cells, they are assisted by helper T cells that secrete small proteins called cytokines to regulate or "help" the immune response.
Given that the proof of principle for the vaccine has been determined, a phase I clinical trial of the vaccine has begun at the University of Pittsburgh Cancer Institute to assess its safety in head and neck cancer patients.
Head and neck cancer accounts for about 5 percent of all newly diagnosed cancers in the United States. More than two-thirds of head and neck cancer patients have a locally advanced stage when diagnosed and have a poor five-year survival rate even after treatment.
Findings were presented at a recent meeting of the American Association for Cancer Research.
Co-authors of the study include Kazuaki Chikamatsu, Ph.D., Koichi Sakakura, Ph.D., and Nobuhiko Furuya, Ph.D., Gunma University School of Medicine in Japan. The study is funded by a grant from the National Institutes of Health.
Materials provided by University of Pittsburgh Schools of the Health Sciences. Note: Content may be edited for style and length.
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