Active vaccination after allogeneic bone marrow cell transplantation: a new option in the immunotherapy of cancer?

The concept of immunotherapy of cancer was 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 fourth option. In this review, we will focus chiefly 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 was recently established in clinical trials that allogeneic bone marrow cell transplantation does not require myeloablative conditioning. Non-myeloabaltive conditioning, which avoids the high toxicity of the conventional approach, it is only kind which allows the recruitment of elderly patients and patients in poor health. 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 antigens. 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, most likely, very powerful tool of cancer therapy. We will briefly summarize current considerations to improve engraftment, and 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 provide 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 will only briefly mention supportive regimen of immunomodulation and those hazards which one is most frequently confronted with in attempts to attack tumors with the inherent weapon of immune defense. Though the successful immunotherapy of cancer still remains far behind expectations, there is a solid basis for the belief that, by improving our understanding of the molecular mechanisms of immunity, this may become a very powerful and less harmful tool than conventional therapies.