A new approach to cancer vaccines, which kills some healthy skin cells to induce a heat shock reaction that kills tumor cells, has eradicated malignant melanoma tumors in mice, according to an article in the August issue of Nature Biotechnology.

The results are especially promising because multiple rounds of treatment eradicated skin cancer in all mice in the study. If this work can be extended to humans, it could have enormous benefits.

This new approach is significant for two reasons: First, It turns the death of healthy cells into a therapeutic advantage by inflicting a stress known as “inflammatory cell death” on skin cells to which researchers attached a protein involved in heat shock. Researchers were able to trigger a healing immune response aimed at the skin cancer tumors. The response was so strong it eradicated the tumors. Researchers were also able to avoid triggering autoimmune attacks, which are a common disabling side effect of most cancer vaccine attempts.

“We’re very encouraged by these results because our main interest is in generating cancer vaccines that will stimulate the immune system to recognize tumors and eradicate them. We hope our novel approach will be a more specific, and therefore gentler therapy for patients,” says Mayo immunologist and lead researcher Richard Vile, Ph.D.

In the first state of work, researchers chose normal melanocytes and created a molecular scout to home in on and kill some melanocytes in mice. To the molecular scout they attached an unusual protein, called heat shock protein 70, or hsp70. It normally is not present in healthy cells, but when cells die under certain conditions, they release hsp70. “It’s a danger-signal system that the body is in trouble,” says Dr. Vile. “We hoped to trigger an anti-tumor response.”

The unanticipated result was a two-step reaction with promising traits that may one day help skin cancer patients. In the first step, the heat shock protein recruited T cells -- the main warriors of the immune system -- that attacked melanocytes. The T cells killed all tumors in the mice.

Researchers also questioned whether a raging T-cell attack might prompt autoimmune disease. The mouse immune system apparently anticipated that. In response to the vaccine, it sent out regulatory T cells to calm down the first group of T cells.

Said Vile: “The nice twist is that originally we thought we would generate a very potent autoimmune disease before we killed the tumor. But we found just the opposite. What happens is that you get a burst of T cells that kill the melanoma, and then they are suppressed by regulatory T cells in the mouse before they cause autoimmune disease.”

For humans, this is good news. “This is very hopeful because we think in the clinic there are good chances we can control anti-tumor effects before we get to the autoimmune problems,” he added.

The researchers will pursue two basic paths. One will extend the current work on a heat shock vaccine to other tissue and tumor types to determine its effectiveness against breast, lung or prostate cancers. The other is to test this immunotherapy in clinical trials with humans.