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The allogeneic graft-versus-cancer effect.
- Source :
-
British journal of haematology [Br J Haematol] 2009 Dec; Vol. 147 (5), pp. 614-33. Date of Electronic Publication: 2009 Sep 04. - Publication Year :
- 2009
-
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.
- Subjects :
- Graft vs Leukemia Effect immunology
Hematopoietic Stem Cell Transplantation trends
Humans
Killer Cells, Natural immunology
Neoplasms immunology
T-Lymphocytes, Cytotoxic immunology
Treatment Outcome
Graft vs Tumor Effect immunology
Hematopoietic Stem Cell Transplantation methods
Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2141
- Volume :
- 147
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 19735262
- Full Text :
- https://doi.org/10.1111/j.1365-2141.2009.07886.x