A group of Italian researchers led by Giorgio Inghirami and Roberto Chiarle, both working at the Cerms laboratory (Center for Experimental Research and Medical Studies) at the Le Molinette hospital in Turin, has discovered a vaccine capable of interfering with the of Alk, an oncogene involved in the transformation of cells in anaplastic lymphoma. The study was published in Nature Medicine. The DNA vaccine has so far been tested on mice genetically modified to develop lymphoma. «An ideal cancer vaccine acts on specific antigens necessary for the survival of the tumor – explains Giorgio Inghirami -. In the case of lymphoma, it is vaccination with person-specific idiotypic immunoglobulin that has shown the most promising results. The study produced a DNA vaccine with plasmids encoding portions of the cytoplasmic domain of anaplastic lymphoma kinase (Alk), previously translocated to several fusion proteins required for anaplastic large cell lymphoma growth. In essence, the vaccine contains an antigen capable of acting against one of the elements characterizing the malignant cells of this blood cancer. Vaccinated mice do not develop the tumor and the protective effect seems to last for the entire life of the rodent. And it is mediated by the production of an Alk-specific interferon-gamma, as well as Cd8 T cell-mediated cytotoxicity. The study went on, in an attempt to demonstrate a curative effect of vaccination. In already sick mice, the vaccine was inoculated before a normal chemotherapy, with the result of eliminating the disease in the majority of cases. «This demonstrates that Alk represents an ideal tumor antigen for a vaccination strategy – continues Inghirami -. And since Alk has also mutated in other human tumors, such as lung cancer, the discovery assumes particular importance". Anaplastic lymphoma is a rare tumour: there are around 2,500 cases in Europe, and the same number in the USA. For this reason, the development phase on humans will be carried out jointly by Cerms of Turin with the MD Anderson Cancer Center of the University of Texas. At the end of the clinical trial, the first oncological vaccine for all tumors with Alk mutations will be available.
Il Sole 24 Ore Sanita' of 16/09/2008 N. 36 – 16-22 SEPTEMBER 2008 p. 16
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