Strategies to enhance anti-tumor immunity : translating preclinical models
- Holbrook E.K. Kohrt.
- Aug. 2012.
- Physical description
- online resource (iii, 209 pages) : illustrations (some color)
- Kohrt, Holbrook E.
- Clarke, Michael F. thesis advisor.
- Levy, Ronald, 1941 December 6- thesis advisor.
- Strober, Samuel. thesis advisor (primary).
- Sunwoo, John B. thesis advisor.
- Stanford University. Program in Cancer Biology.
- Stanford University. Committee on Graduate Studies. degree grantor.
- Includes bibliographical references.
- Purpose: The immune modulatory effects of total lymphoid irradiation (TLI) for graft-versus-host disease (GVHD) protection and transplantation tolerance following allogeneic bone marrow and organ transplantation have been studied for years in animal models. In preclinical models non-myeloablative TLI conditioning alters residual host T cell subsets to favor regulatory natural killer (NK) T cells that suppress GVHD and prevent organ allograft rejection. These preclinical models have been recently adapted to human transplantation. Recent findings: Patients receiving allogeneic hematopoietic cell transplantation (HCT) for hematological malignancies conditioned with TLI and depletive T cell antibodies showed sustained donor chimerism, a reduced incidence of acute GVHD yet retained graft anti-tumor activity. As in the pre-clinical models, nonmyeloablative TLI conditioning significantly altered residual host T cell subsets favoring NK T cells, and the low incidence of GVHD was associated with increased IL-4 secretion by chimeric donor T cells. The TLI regimen used in cancer patients was modified to determine conditions for stable mixed chimerism and tolerance induction following combined hematopoietic cell and kidney transplantation. Summary: This review summarizes the evolution of the pre-clinical TLI protocols and their recent translation to clinical trials, and discusses the mechanisms involved in protection from GVHD and the induction of tolerance following mixed chimerism.
- Bone Marrow Transplantation
- Graft vs Host Disease > immunology
- Hematopoietic Stem Cell Transplantation
- Lymphatic Irradiation
- T-Lymphocyte Subsets > transplantation
- Publication date
- Submitted to the Program in Cancer Biology and the Committee on Graduate Studies of Stanford University.
- Thesis (Ph.D.)--Stanford University, 2012.