Active vaccination after allogeneic bone marrow cell transplantation: a new option in the immunotherapy cancer?
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The concept of immunotherapy of cancer has been evoked more than a century ago by W. Coley. Yet, it is only recently that the state of knowledge allows for molecularly defined therapeutic approaches and much effort will still be required to place immunotherapy beside of surgery, chemotherapy and radiation as a forth option. In this review, we will strongly focus on two aspects: active therapeutic vaccination, because it is our belief that this approach will provide a major breakthrough and the potential efficacy of combining active vaccination with allogeneic bone marrow cell transplantation. It lately could be established in clinical trials that allogeneic bone marrow cell transplantation does not require myeloablative conditioning. Only non-myeloabaltive conditioning, which avoids the high toxicity of the conventional approach, allows the recruitment of elderly patients and patients in poor health condition. Concerning active vaccination protocols we will address the questions 1) what the targets (i.e. the antigens) of immunotherapeutic approaches could be; 2) how to achieve an optimal confrontation of the immune system with these tumor-associated antigens; and 3) which response elements are needed for raising a therapeutically successful immune reaction against these. Many question remain to be answered in the field of allogeneic bone marrow transplantation after non-myelablative conditioning to optimize the therapeutic setting for this likely very powerfull tool of cancer therapy. We will briefly summarize current considerations to improve engraftment, to reduce graft versus host disease while strengthening graft versus tumor reactivity. There is some hope that the latter can be 'naturally' maintained during the process of T cell maturation in the allogeneic host. Provided this hypothesis can be substantiated, the efficacy of active vaccination of the allogeneically reconstituted host will meet a pool of virgin T cells, which are tolerant towards the host, but not anergized towards tumor antigens presented by MHC molecules of the host. We only briefly will mention suportive regimen of immunomodulation and those hazards which one is most frequently confronted with in trials to attack tumors with the inherent weapon of immune defense. Though successful immunotherapy of cancer still remains far behind expectation, there is a solid basis to believe that by improving our understanding of molecular mechanisms of immunity, it may become a very powerful and less harmful tool than conventional therapies.
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M. Zoller, Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany