Gene therapy of cancer using an interleukin 2 transmembrane construct

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Title Gene therapy of cancer using an interleukin 2 transmembrane construct
Publication Type thesis
School or College School of Medicine
Department Pathology
Author Adams, Nathan Bradley
Date 2002-12
Description Selective expression of cytokines on the surface of tumors is likely to stimulate tumor-infiltration lymphocytes that are primed and already recognize tumor antigens. This may result in enhanced tumor recognition and killing. This gene therapy approach may avoid toxicity associated with systemic therapy with high doses of the cytokines needed to achieve the same effects. In order to test this concept, we have evaluated an IL-2 gene construct that is designed to induce tumor cells to express a membrane bound form of IL-1 (IL-2tm). A mammalian plasmid expression vector was designed to express a fusion gene consisting of human interleukin 2 with Fc-epsilon-gamma transmembrance anchor derived from a subunit of the FC epsilon receptor. We demonstrated that mRNA and protein for the IL-2tm fusion protein was expressed in transfected RD995 tumor cells. Expression of the IL-2tm protein on the tumor cell surface membrane was confirmed by laser confocal microscopy. In order to assess biological function, RF995 transfected with IL-2tm or pCMV2b (empty expression vector) were implanted subcutaneously into C3H/HEN mice. Non-transfected RD995 was also implanted subcutaneously for tumor growth comparison (control group). RD998 tumor cells (10[6] or 10[5]/mouse) transfected with IL-2tm grew more slowly than RD995 transfected with pCMV2b or non-transfected control RD995 implanted tumors after implantation into syngenic animals. Further preclinical evaluation of the IL-2tm gene therapy as a possible cancer treatment is underway.
Type Text
Publisher University of Utah
Subject Genetics; RNA
Subject MESH Receptors, Interleukin-2; Gene Therapy; Neoplasms
Dissertation Institution University of Utah
Dissertation Name MS
Language eng
Relation is Version of Digital reproduction of "Gene therapy of cancer using an interleukin 2 transmembrane construc." Spencer S. Eccles Health Sciences Library. Print version of "Gene therapy of cancer using an interleukin 2 transmembrane construce." available at J. Willard Marriott Library Special Collection. RC39.5 2002 .A33.
Rights Management © Nathan Bradley Adams.
Format application/pdf
Format Medium application/pdf
Format Extent 624,916 bytes
Identifier undthes,5364
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 624,966 bytes
ARK ark:/87278/s6m90bdq
Setname ir_etd
ID 190547
Reference URL https://collections.lib.utah.edu/ark:/87278/s6m90bdq
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