Chemo-Immunotherapy of Murine Cancer Using Alpha Tocopheryl Succinate and Non-Matured Dendritic Cells

Persistent Link:
http://hdl.handle.net/10150/194412
Title:
Chemo-Immunotherapy of Murine Cancer Using Alpha Tocopheryl Succinate and Non-Matured Dendritic Cells
Author:
Ramanathapuram, Lalitha
Issue Date:
2006
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The search for anticancer drugs that are tumor specific and cause minimal side effects and the development of effective cancer vaccines are focal points of cancer therapy today. Dendritic cells (DC) are considered potential candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness in abrogating established tumors in mice and human cancer patients. The use of appropriate adjuvants can enhance the efficacy of DC-based cancer vaccines in treating established tumors.The studies in this dissertation describe a chemo-immunotherapeutic strategy, which combines a Vitamin E analog, a-tocopheryl succinate (a-TOS) that is selectively toxic to tumor cells with non-antigen pulsed, non-matured dendritic cells (nmDC) to treat established murine lung and breast tumors. The results demonstrate that a-TOS synergizes with nmDC to inhibit the growth of established tumors and significantly reduce residual lung metastasis when therapy is initiated after surgical removal of primary tumors. This outcome was correlated with increased IFN-g and IL-4 production by splenic and draining lymph node lymphocytes. In trying to understand the mechanism of action of the combination treatment we observed that a-TOS treated tumor cells factors cause DC maturation in vitro. This effect is mediated in part by heat shock proteins 60, 70 and 90 induced during a-TOS-mediated killing of tumor cells. This study demonstrates the potential usefulness of a-tocopheryl succinate, an agent non-toxic to normal cell types, as an adjuvant to augment the effectiveness of DC-based vaccines in treating cancer.
Type:
text; Electronic Dissertation
Keywords:
Dendritic cells; Alpha-tocopheryl succinate; Cancer
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Microbiology & Immunology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Akporiaye, Emmanuel T.
Committee Chair:
Akporiaye, Emmanuel T.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleChemo-Immunotherapy of Murine Cancer Using Alpha Tocopheryl Succinate and Non-Matured Dendritic Cellsen_US
dc.creatorRamanathapuram, Lalithaen_US
dc.contributor.authorRamanathapuram, Lalithaen_US
dc.date.issued2006en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe search for anticancer drugs that are tumor specific and cause minimal side effects and the development of effective cancer vaccines are focal points of cancer therapy today. Dendritic cells (DC) are considered potential candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness in abrogating established tumors in mice and human cancer patients. The use of appropriate adjuvants can enhance the efficacy of DC-based cancer vaccines in treating established tumors.The studies in this dissertation describe a chemo-immunotherapeutic strategy, which combines a Vitamin E analog, a-tocopheryl succinate (a-TOS) that is selectively toxic to tumor cells with non-antigen pulsed, non-matured dendritic cells (nmDC) to treat established murine lung and breast tumors. The results demonstrate that a-TOS synergizes with nmDC to inhibit the growth of established tumors and significantly reduce residual lung metastasis when therapy is initiated after surgical removal of primary tumors. This outcome was correlated with increased IFN-g and IL-4 production by splenic and draining lymph node lymphocytes. In trying to understand the mechanism of action of the combination treatment we observed that a-TOS treated tumor cells factors cause DC maturation in vitro. This effect is mediated in part by heat shock proteins 60, 70 and 90 induced during a-TOS-mediated killing of tumor cells. This study demonstrates the potential usefulness of a-tocopheryl succinate, an agent non-toxic to normal cell types, as an adjuvant to augment the effectiveness of DC-based vaccines in treating cancer.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectDendritic cellsen_US
dc.subjectAlpha-tocopheryl succinateen_US
dc.subjectCanceren_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineMicrobiology & Immunologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorAkporiaye, Emmanuel T.en_US
dc.contributor.chairAkporiaye, Emmanuel T.en_US
dc.contributor.committeememberKatsanis, E.en_US
dc.contributor.committeememberLybarger, L.en_US
dc.contributor.committeememberMarchalonis, J.en_US
dc.identifier.proquest1661en_US
dc.identifier.oclc137356656en_US
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