Therapeutic Cancer Vaccines have the potential to become curative therapies for metastatic cancer.Of available cancer treatment technologies, including surgery, radiation, chemotherapy, monoclonal antibodies and small molecule targeted therapies, only the immune system has the technological capability of eliminating the last tumor cell.If the immune system can be harnessed, it has the capability to eliminate large tumor burdens and has the fine specificity to eliminate microscopic disease wherever it might reside in the body.Further, only the immune system has the capability of memory, which in theory would enable vaccinated patients to be protected from recurring disease without further intervention.However, despite the promising results in animal tumor models, the clinical results has been disappointing.I believe that the reason for these disappointing results is due to immunotherapy drug designs being based upon underlying assumptions that are incorrect.Immunotherapy design strategies are generally based on one or both of the following assumptions: (1) cancer is a disease of a weak immune system and thus treatment requires immune boosting strategies;and/or (2) cancer cells are weakly immunogenic because they are derived from self tissues and thus treatment requires strategies to improve the immunogenicity.In this presentation, I will present evidence which questions these long held beliefs about how the immune system interacts with tumors.Instead of using animal models,I will discuss a human model of immune-mediated cancer elimination that has been proven and is widely accepted.This is the immune mechanism of non-myeloablative allogeneic stem cell transplant procedures which are proven to enable debulking and elimination of chemotherapy-resistant metastatic tumors.This anti-tumor immune effect, known as the "graft vs.tumor" (GVT) effect, has been described as the most powerful anti-cancer mechanism ever discovered.Unfortunately, this beneficial GVT effect is intimately related to graft vs.host disease (GVHD) toxicity which limits the clinical application of GVT.I propose a strategy which reverse engineers the related GVT and GVHD effects that emanate from the graft so that they instead emanate from the host.I present a bioengineered allograft designed to elicit a host vs.tumor (HVT) effect identical to the GVT effect and intimately related to a rejection of the allograft (HVG).I then will present clinical data from a Phase Ⅰ/Ⅱ clinical trial using this bioengineered allograft demonstrating radiological, pathological and immunological evidence of tumor debulking of metastatic cancers without conditioning,tissue matching or GVHD.