1. New immunogenetic approaches for innovative vaccines and immunotherapies against cancer. Our research is focussed on the genetic modification of tumor cells by introducing the MHC class II transactivator gene (CIITA), discovered in our laboratory, to render tumor cells MHC class II positive and in this way, potential antigen presenting cells for their own tumor antigens to CD4 T cells, the immune subpopulation that is absolutely required for triggering all the effector mechanism (CTL and B cells) against cancer 2. Interactions between retroviruses (HIV and HTLV) and infected cells. We have discovered that CIITA not only upregulates MHC class II gene expression, thus controlling the initial phase of adaptive immune response, but also inhibits directly HIV and Human oncogenic retrovirus HTLV replication in infected cells. Our interest is therefore focussed toward the construction of a suitable methodology to activate endogenous CIITA or to transfer CIITA by appropriate vectors into retrovirus infected cells. We hope in this way to block viral spreading in HIV-infected patients and to counteract the oncogenic transformation of cells infected by HTLV. Targeting innate immunity in anti-angiogenic cancer therapy Within the tumor microenvironment, host components including endothelial andstromal cells, as well as immune infiltrates, represent key therapeutic targets. Clinical inhibition of tumor vascularization with specific agents significantly prolongs patient survival for diverse tumor types; however, the clinical benefit is as yet in terms of months. An indicator of the importance of innate immunity in controlling angiogenesis is our discovery that the endogenous angiogenesis inhibitor, angiostatin, has immune cells as a primary target and requires immune cell derived IL-12. We are investigating the action of angiostatin on immune cells, particularly regarding phenotype switching and mechanisms.