Immunotherapy of cancer by active vaccination: does allogeneic bone marrow transplantation after non-myeloablative conditioning provide a new option?

Abstract

The critical role of antigen-specific T cells in cancer immunotherapy has been amply demonstrated in many model systems. Though success of clinical trials still remains far behind expectation, the continuous improvement in our understanding of the biology of the immune response will provide the basis of optimized cancer vaccines and allow for new modalities of cancer treatment. This review focuses on the current status of active therapeutic vaccination and future prospects. The latter will mainly be concerned with allogeneic bone marrow cell transplantation after non-myeloablative conditioning, because it is my belief that this approach could provide a major breakthrough in cancer immunotherapy. Concerning active vaccination protocols the following aspects will be addressed: i) the targets of immunotherapeutic approaches; ii) the response elements needed for raising a therapeutically successful immune reaction; iii) ways to achieve an optimal confrontation of the immune system with the tumor and iv) supportive regimen of immunomodulation. Hazards which one is most frequently confronted with in trials to attack tumors with the inherent weapon of immune defense will only be briefly mentioned. Many question remain to be answered in the field of allogeneic bone marrow transplantation after non-myeloablative conditioning to optimize the therapeutic setting for this likely very powerful tool of cancer therapy. Current considerations to improve engraftment and to reduce graft versus host disease while strengthening graft versus tumor reactivity will be briefly reviewed. Finally, I will discuss whether tumor-reactive T cells can be "naturally" maintained during the process of T cell maturation in the allogeneic host. Provided this hypothesis can be substantiated, a T cell vaccine will meet a pool of virgin T cells in the allogeneically reconstituted host, which are tolerant towards the host, but not anergised towards tumor antigens presented by MHC molecules of the host.