Strategies to enhance anti-tumor immunity : translating preclinical models
Abstract/Contents
- 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.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Kohrt, Holbrook E | |
|---|---|---|
| Associated with | Stanford University, Cancer Biology Program. | |
| Primary advisor | Strober, Samuel | |
| Thesis advisor | Strober, Samuel | |
| Thesis advisor | Clarke, Michael F | |
| Thesis advisor | Levy, Ronald, 1941 December 6- | |
| Thesis advisor | Sunwoo, John B | |
| Advisor | Clarke, Michael F | |
| Advisor | Levy, Ronald, 1941 December 6- | |
| Advisor | Sunwoo, John B |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Holbrook E. K. Kohrt. |
|---|---|
| Note | Submitted to the Program in Cancer Biology. |
| Thesis | Ph.D. Stanford University 2012 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Holbrook Kohrt
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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