February 16, 2010

Cancer Vaccine Progress and Nanoparticles in Cellular Nuclei to kill Cancer

1. Researchers at National Jewish Health and the University of Colorado School of Medicine have used a new strategy to develop cancer vaccines that are remarkably effective in mice. In the February 16 issue of the Proceedings of the National Academy of Sciences (PNAS), Kimberly Jordan, PhD, Jill Slansky, PhD, and John Kappler, PhD, report that 100 percent of the mice vaccinated with a peptide they developed remained alive and tumor-free for at least 60 days after inoculation with colon cancer cells. The research suggests a method for developing vaccines against a wide variety of cancers.

They vaccinated mice twice with the candidate vaccines, then injected colon tumor cells into the mice a week later. The results were quite variable. Two of the vaccines protected few or no mice, three other vaccines kept 60%, 90% and 100% alive and tumor-free for 60 days.

The researchers tried to learn what distinguished the effective peptide vaccines from ineffective ones. They found that the ineffective vaccines strongly stimulated T cells that recognized the peptide vaccine but not any T cells that recognized antigen on the cancer cells.

The successful vaccines stimulated T cells that recognized both the peptide vaccine and the naturally occurring antigen. The successful antigens stimulated the growth of many more T cells than the ineffective ones. Those T cells were also highly activated and ready to attack, as evidenced by their production of cytokine signaling molecules. Remarkably, the most successful vaccine varied by only one amino acid from the naturally occurring antigen, which provoked almost no immune response.

"Our theory about the importance of the T cell-peptide bond was correct, but we learned that the peptides must also stimulate T cells that cross react with the existing antigens and produce a large population of activated T cells," said Dr. Kappler. "We believe this provides a very promising strategy for developing cancer vaccines. We are now working to learn why a single-amino-acid substitution makes such a huge difference in effectiveness."

2. Scientists at the Georgia Institute of Technology have shown that by directing gold nanoparticles into the nuclei of cancer cells, they can not only prevent them from multiplying, but can kill them where they lurk. The research appeared as a communication in the February 10 edition of the Journal of the American Chemical Society.

The team tested their hypothesis on cells harvested from cancer of the ear, nose and throat. They decorated the cells with an argininge-glycine-aspartic acide petipde (RGD) to bring the gold nano-particles into the cytoplasm of a cancer cell but not the healthy cells and a nuclear localization signal peptide (NLS) to bring it into the nucleus.

In previous work they showed that just bringing the gold into the cytoplasm does nothing. In this current study, they found that implanting the gold into the nucleus effectively kills the cell.

“The cell starts dividing and then it collapses,” said El-Sayed. “Once you have a cell with two nuclei, it dies.” The gold works by interfering with the cells’ DNA, he added. How that works exactly is the subject of a follow-up study.

“Previously, we’ve shown that we can bring gold nanoparticles into cancer cells and by shining a light on them, can kill the cells. Now we’ve shown that if we direct those gold nanoparticles into the nucleus, we can kill the cancer cells that are in spots we can’t hit with the light,” said El-Sayed.

Next the team will test how the treatment works in vivo

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