Researchers from the University of Pittsburgh and the Gunma University School of Medicine have developed a vaccine that enlists multiple parts of the immune system into targeting p53 in head and neck squamous cell cancer.
A phase I clinical trial of the vaccine is currently underway at the University of Pittsburgh Cancer Institute.
According to researchers, this is the first vaccine that takes a multi-pronged approach to stimulating the immune system with derivatives of wild type ? or non-altered ? p53, a tumor suppressor gene. Loss of suppressor function or alteration of the p53 gene factors into nearly 80 percent of human tumors. Tumor cells with altered p53 generally tend to accumulate the protein, which led the researchers to create a strategy that would allow the immune system to destroy tumor cells by targeting p53.
“Instead of creating a vaccine based on mutant p53, which would require a custom vaccine for every patient, our strategy is to target parts of the unaltered p53 protein that can best activate the immune system,” said Theresa Whiteside, Ph.D., professor at the University of Pittsburgh School of Medicine. “We are using different unaltered portions of the p53 molecule to entice the immune system into attacking tumors.”
According to the investigators, their vaccine uses three different p53-derived peptides to elicit responses from different aspects of immune system. The vaccine currently in trial uses autologous (patients? own) dendritic cells (DC) pulsed with a combination of three peptides: two that trigger cytotoxic T cells, which directly kill targeted tumor cells, and one peptide that stimulates helper T cells.
Altogether, it is an approach that not only excites the killer T cells into action, but also influences the helper T cells, which are instrumental in sustaining the killer T-cell response. The combined strategy has already shown great promise in studies using animal models and human cells in culture, according to the researchers.
The phase I trial, which will eventually enroll 24 patients with head and neck cancer, has three experimental arms, each including a DC-based vaccine containing p53-derived T cell-specific peptides. The three groups vary on whether the cytotoxic p53 peptides are delivered alone or in combination with a helper T cell-activating peptide that is either specific to p53 or not specific to p53.
“Despite great medical progress, the survival rate in head and neck cancer still remains very poor, at about 50 percent, and there is a definite need for new treatment modalities like vaccination,” Whiteside said. “Targeting of p53, however, is a strategy that could also work in treating a number of different cancer types, since p53 loss of function is such a common feature of many cancers.”