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

Included in

Physiology Commons

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