Over the past decade, knowledge of the way in
which the immune system can be used to fight cancer has greatly
increased. Not only have scientists learned that the immune system
can recognize certain proteins on cancer cells, but they have used
this knowledge to develop vaccines that may help prevent cancer recurrence.
Now, scientists at Memorial Sloan-Kettering Cancer Center in New York
have demonstrated that a new DNA-based vaccine can successfully treat
melanoma in mice. The investigators, who reported their findings in
the September 16th issue of the Journal of Clinical Investigation,
used a "needleless syringe" called a gene gun to drive tiny
particles of human DNA at high speed into the skin of the mice. The
human protein differed just enough from its mouse counterpart to
trick the immune system into producing a powerful immune assault. The
immune cells attacked both the melanoma cells and the pigment cells
(which share a protein called gp75 that is not found in other tissues).
Engineering the Immune System
"Our study shows how we can use DNA immunization to make the
immune system recognize and attack cancer cells," said Dr. Alan
Houghton, chief of the Clinical Immunology Service at Memorial
Sloan-Kettering and senior author of the study. The same strategy is
being tested against prostate, breast, and lymphoma cancers in mice,
which also share specific proteins with their normal cell
counterparts. "These DNA vaccines are unique because they can
trigger immunity where other types of vaccines fail to stimulate an
immune response," said Dr. Houghton, noting that they are easy
to produce, handle, and store.
The mice were immunized with human DNA via a novel delivery system
called a gene gun. Microscopic gold particles were coated with human
DNA and injected into the skin of the mice using a burst of helium
gas. Once inside the skin cells, the DNA triggered an immune response.
Mouse vs Human DNA
In the study, Dr. Houghton and his research team attempted to induce
an immune attack by using the gene gun to immunize the mice with
either a purified form of mouse DNA or the human DNA. When the
investigators later examined the lungs of the mice that had received
mouse DNA, they found that the tumors were widespread and no immune
response could be detected. However, in the mice injected with human
DNA, the tumors had regressed by 86% and there was a marked immune response.
In addition to inducing an immune attack in the mice, researchers
found that the human DNA also caused an autoimmunity reaction similar
to vitiligo in humans: white patches on the otherwise dark fur of the
mice. Vitiligo occasionally develops in melanoma patients and may be
indicative of a good outcome.
"Our goal was to induce a very controlled autoimmune response
that would lead to protection against the tumor spreading," said
Dr. Houghton. "The human DNA induced an autoimmune response that
prevented the tumor from spreading, and as a side effect, destroyed
Although immunologists know that autoimmunity can accompany an immune
response, Dr. Houghtons team found that the mechanisms involved
in immune responses against tumors vs autoimmunity against normal
tissues were quite different. "This means that we may be able to
vaccinate a patient against melanoma, and thus induce an immune
response against the tumor while, at the same time, blocking any
autoimmunity from ever occurring," explained Dr. Houghton.
Dr. Houghtons research team plans to begin clinical trials
using DNA from mice in melanoma patients some time next year.