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Gene vaccine protects mice against development of Her2/neu breast cancer

AlphaVax, Inc., a privately held biotechnology company in Research Triangle Park, N.C., have deleted certain genes from the VEE virus, thereby making it impossible for the vector version of virus to reproduce itself, but still allowing the vector to express the target protein. For this study, the researchers inserted the gene for the HER2/neu protein in place of the deleted viral genes and then packaged the virus vector into virus-like replicon particles, referred to as "VRP-neu." When these non-propagating particles are injected into an animal, the vector directs the animal's cells to make thousands of copies of the HER2/neu growth protein, says Lachman.

In addition, the VRP-neu preferentially homes to specialized immune system cells known as dendritic cells, and infects them. Inside, VRP-neu produces high levels of the HER2/neu protein, which the dendritic cells then display on the outside of their cell surface. This is, in fact, a neat trick, says Lachman, because the function of dendritic cells is to flag the immune system by presenting "antigen," or pieces of a foreign invader, to activate an immune response. "So now, the same immune system cells that rev up the immune system are displaying HER2/neu proteins as antigens," Lachman says.

What results is a strong response against HER2/neu that incorporates all three arms of the immune system - B cell, T cell and natural killer cells - and which creates a long-lasting immune memory primed to attack breast cancer cells that are studded with HER2/neu proteins, he says.

In the experiments, three groups of seven mice were treated with three injections of a vaccine. The "control" arm received a VRP vaccine that contained an influenza protein, and the other two groups received one of two different doses of the VRP-neu vaccine. Researchers then implanted a HER2/neu-positive tumor into mammary tissue in the mice. All of the control mice developed breast cancer but only one mouse in each of the VRP-
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Contact: Julie A. Penne
jpenne@mdanderson.org
713-792-0655
University of Texas M. D. Anderson Cancer Center
10-Jan-2005


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