Induction of Tumor Immunity Following Allogeneic Stem Cell Transplantation

Cancer Vaccine Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Advances in Immunology (Impact Factor: 5.96). 02/2006; 90:133-73. DOI: 10.1016/S0065-2776(06)90004-2
Source: PubMed


The curative potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for many hematologic malignancies derives in large part from reconstitution of normal donor immunity and the development of a potent graft-versus-leukemia (GVL) immune response capable of rejecting tumor cell in vivo. Elucidation of the mechanisms of GVL by studies of animal models and analysis of clinical data has yielded important insights into how clinically effective tumor immunity is generated following allo-HSCT. These studies have identified NK cells and B cells as well as T cells as important mediators of the GVL response. A variety of antigenic targets of the GVL response have also been identified, and include tumor-associated antigens as well as minor histocompatibility antigens. The principles of effective GVL can now be applied to the development of novel therapies that enhance the therapeutic benefit of allogeneic HSCT while minimizing the toxicities associated with treatment. Moreover, many components of this approach that result in elimination of tumor cells following allogeneic HSCT can potentially be adapted to enhance the effectiveness of tumor immunity in the autologous setting.

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    • "However, the majority of allo-HCT procedures are performed for patients with leukemias, lymphomas and other clonal hematological disorders. In these cases, the allogeneic graft provides T cells and other immune cells that play major therapeutic roles through recognition and elimination of cancer cells in the host (graft-versus-tumor, or GVT, effect) [3] [4] [5]. Unfortunately, donor-derived T cells also lead to immune-mediated damage in normal host tissues, a life-threatening complication referred to as graft-versushost disease (GVHD) [6] [7] [8]. "
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    • "Second, DZNep has broad and potent antiviral activity, including against vesicular stomatitis virus, rotavirus, and vaccinia virus (30, 31). In particular, this antiviral spectrum of DZNep extends to human cytomegalovirus (31), which causes serious infection in patients after organ transplantation (32). Third, DZNep has been investigated as an effective therapy in mice model target on PRC2 to treat the breast cancer (20, 33), acute myeloid leukemia (34), glioblastoma (35), and so on. "
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