Antigen specific tumor immuno-therapy with lentivirus transduced hematopoietic stem cells for transplant

Extract: Immunotherapeutic approaches to tumors have shown generally disappointing clinical results. The goal of the studies presented in this report was to demonstrate a novel approach to tumor immunology in which new techniques were employed to bypass some of the major limitations that have been observed in tumor immunotherapies. Many tumor types express antigens that can be useful targets for the immune system if properly recognized, but tumors have developed means of generating immunological resistance. The studies were designed to generate a potent anti-tumor immune response by manipulating tumor antigen presentation to tumor-reactive T cells such that the immune system would recognize and destroy tumor cells. Towards this end, experiments were designed to address limitations in the previous approaches to tumor vaccines using dendritic cells (DCs) as vehicles. While DCs are potent antigen presenting cells and have been shown to stimulate T cells that are reactive to tumors, efficacy of them in clinical trials as vaccines has left room for improvement. Previous results from trials using ex vivo generated dendritic cells that have been loaded with antigen have shown that while immune responses to antigens can be generated, the ex vivo generated DCs do not efficiently traffic to secondary lymphoid organs. Studies conducted in mouse models suggest that this may be a result of both inefficient trafficking and elimination of the injected DCs by host T cells. A different approach for antigen-loaded DCs, namely, in vivo transfer of antigen has shown that it is difficult to effectively load DCs with antigen in vivo, and in both methods, a small percentage of antigen-loaded DCs were found in the lymph nodes.