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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

AUGMENTATION OF T CELL EXPANSION FOR ADOPTIVE IMMUNOTHERAPY BY ALTERNATE GAMMA CHAIN CYTOKINES AND BY GEMCITABINE MEDIATED INHIBITION OF MYELOID DERIVED SUPPRESSOR CELLS

Le, Hanh 01 January 2008 (has links)
Successful treatment of cancer with adoptive immunotherapy (AIT) is dependent on the ability to produce large numbers of tumor-specific, functional T cells. The purpose of this thesis is to explore ways in which T cell expansion could be augmented. We have focused on exploring alternate gamma chain cytokines as stimulators of T cell proliferation and differentiation in addition to investigating the potential usefulness of gemcitabine (GEM) in abrogating the immunosuppressive effects of myeloid derived suppressor cells (MDSCs). B16 melanoma sensitized draining lymph node cells that have been activated in vitro with bryostatin-1 and ionomycin (B/I) were expanded in either IL-7/15 or in IL-2. We found that IL-7/15 was superior to IL-2 in expanding T cells for AIT of pulmonary metastases. Expansion of antitumor T cells was also improved by suppressing accumulation of MDSCs in mice bearing 4T1 mammary carcinoma using GEM. GEM directly inhibits both 4T1 mammary carcinoma cells and MDSCs. Its inhibition of MDSCs rescued tolerant T cells, augmenting both expansion and response to tumor antigen.

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