title: The allogeneic graft-versus-cancer effect.
abstract: Allogeneic haematological stem cell transplantation (HSCT) has developed into immunotherapy. Donor CD4+, CD8+ and natural killer (NK) cells have been reported to mediate graft-versus-leukaemia (GVL) effects, using Fas-dependent killing and perforin degranulation to eradicate malignant cells. Cytokines, such as interleukin-2, interferon-gamma and tumour necrosis factor-alpha potentiate the GVL effect. Post-transplant adoptive therapy of cytotoxic T-cells (CTL) against leukaemia-specific antigens, minor histocompatibility antigens, or T-cell receptor genes may constitute successful approaches to induce anti-tumour effects. Clinically, a significant GVL effect is induced by chronic rather than acute graft-versus-host disease (GVHD). An anti-tumour effect has also been reported for myeloma, lymphoma and solid tumours. Reduced intensity conditioning enables HSCT in older and disabled patients and relies on the graft-versus-tumour effect. Donor lymphocyte infusions promote the GVL effect and can be given as escalating doses with response monitored by minimal residual disease. A high CD34+ cell dose of peripheral blood stem cells increases GVL. There is a balance between effective immunosuppression, low incidence of GVHD and relapse. For instance, T-cell depletion of the graft increases the risk of relapse. This paper reviews the current knowledge in graft-versus-cancer effects. Future directions, such as immunotherapy using leukaemia-specific CTLs, allo-depleted T-cells and suicide gene manipulated T-cells, are presented.
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation and Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. Olle.Ringden@ki.se
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.forename: Helen
authors.initials: H
authors.lastname: Karlsson
authors.forename: Richard
authors.initials: R
authors.lastname: Olsson
authors.forename: Brigitta
authors.initials: B
authors.lastname: Omazic
authors.forename: Michael
authors.initials: M
authors.lastname: Uhlin
mesh_terms: D020544:Graft vs Leukemia Effect / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome