DOI
https://doi.org/10.25772/G9YP-0R53
Defense Date
2009
Document Type
Thesis
Degree Name
Master of Science
Department
Physiology
First Advisor
Harry Bear
Abstract
Successful adoptive immunotherapy (AIT) for cancer relies on the infusion of in vitro expanded, tumor-reactive lymphocytes with a goal of generating productive tumor immunity. Previously, our lab has developed a protocol to activate selectively tumor-reactive T lymphocytes in vitro using two pharmacologic agents, bryostatin-1 and ionomycin. Following the pharmacological stimulation, conventionally, IL-2 is added to stimulate in vitro proliferation. In this report, alternate cytokines from the common cytokine receptor γ-chain family, namely IL-7 and IL-15, were explored as the alternative cytokine supplements. We found that tumor DLN cells activated in vitro with B/I and cultured in IL-7/15 alternate common γ-chain cytokines expanded better than IL-2 cultured cells. Furthermore, immunosuppressive myeloid-derived suppressor cells from the tumor microenvironment were targeted with a chemotherapeutic agent, gemcitabine. Despite combining gemcitabine and the T lymphocytes expanded in IL-7/15, AIT failed to induce regression of large established 4T1 mammary flank tumors.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
August 2009