Adoptive immunotherapy in canine and human chimeras

H. J. Kolb, E. Holler, M. Schleuning, G. Ledderose, J. Mittermüller, H. Menzel, M. Schumm, W. Gunther, A. Schattenberg, D. Bunjes, J. M. Goldman, N. Jacobsen, P. Ljungman

Research output: Contribution to journalArticlepeer-review

Abstract

The chimeric state provides a unique opportunity for adoptive immunotherapy with donor cells. Studies in dogs have shown that two months after transplantation of marrow from DLA-identical littermate dogs stable transplantation tolerance is established. Graft-versus-host disease is prevented by depletion of T-cells, and mixed chimerism can be induced by transfusion of a low number of marrow cells. Transfusion of donor lymphocytes converts mixed into complete chimerism Immunity to tetanus toxoid can be transferred from the donor to the host, and the reactivity of the host to diptheria toxoid can be improved by transfusion of donor lymphocytes. In patients with relapsing leukemia complete remissions can be induced by the transfusion of donor lymphocytes The effect of donor lymphocyte transfusions is best in patients with chronic myelogenous leukemia and hematologic relapse or cytogenetic relapse, less frequent in patients with acute myeloid leukemia and myelodysplastic syndrome, and least in patients with acute lymphoblastic leukemia. Graft-versus-host disease and myelosuppression are complications of this treatment. The target antigens of these graft-versus-leukemia reactions are not known, minor histocompatibility antigens probably play a major role. Mechanisms of immune escape of leukemia cells are discussed. The addition of antigen presenting cells derived from stem cells is studied. Adoptive immunotherapy in chimeras offers new possibilities for the treatment of leukemia and viral infections.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalCancer Research Therapy and Control
Volume9
Issue number1-2
StatePublished - 1999
Externally publishedYes

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