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Strategies to enhance anti-tumor immunity : translating preclinical models

Author: Holbrook KohrtSamuel StroberMichael ClarkeRonald LevyJohn B SunwooAll authors
Publisher: 2012.
Dissertation: Ph. D. Stanford University 2012
Edition/Format:   Thesis/dissertation : Document : Thesis/dissertation : eBook   Computer File : English
Summary:
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  Read more...
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Details

Genre/Form: Academic theses
Material Type: Document, Thesis/dissertation, Internet resource
Document Type: Internet Resource, Computer File
All Authors / Contributors: Holbrook Kohrt; Samuel Strober; Michael Clarke; Ronald Levy; John B Sunwoo; Stanford University. Cancer Biology Program.
OCLC Number: 809415904
Notes: Submitted to the Program in Cancer Biology.
Description: 1 online resource
Responsibility: Holbrook E.K. Kohrt.

Abstract:

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.

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