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  • Improving the Potency of a Melanoma Vaccine by Using a Third Co-Stimulatory Molecule

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    Powell_2013_01Thesis.pdf (4.562Mb)
    Author(s)
    Powell, Katie
    Primary Supervisor
    Ralph, Steve
    Other Supervisors
    Kelly, Pauline
    Year published
    2013
    Metadata
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    Abstract
    Melanoma is the third most commonly diagnosed form of cancer amongst Australians and Australia has the highest incidence of melanoma in the world. At present, there are no vaccines that are approved for the treatment of melanoma. Previous research performed in the laboratory resulted in the development of a syngeneic, whole cell melanoma vaccine engineered to express high levels of the B7.1 T cell co-stimulatory molecule, in addition to using high doses of interferons to upregulate MHC Class I molecules on the surface of the vaccine cells. Results from extensive mouse trials determined that the incorporation of B7.1 into the ...
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    Melanoma is the third most commonly diagnosed form of cancer amongst Australians and Australia has the highest incidence of melanoma in the world. At present, there are no vaccines that are approved for the treatment of melanoma. Previous research performed in the laboratory resulted in the development of a syngeneic, whole cell melanoma vaccine engineered to express high levels of the B7.1 T cell co-stimulatory molecule, in addition to using high doses of interferons to upregulate MHC Class I molecules on the surface of the vaccine cells. Results from extensive mouse trials determined that the incorporation of B7.1 into the vaccine cell model directly stimulated CD8+ T cells to effectively kill melanoma cells in CTL assays and protect mice from developing tumours following injection with live tumour cells expressing intermediate levels of B7.1, thereby replacing the requirement for CD4+ T cells. Subsequently, the vaccine technology was translated into a human allogeneic, whole cell vaccine that completed testing in 2011 on stage IV melanoma patients in a Phase I clinical trial at the Princess Alexandra Hospital, Brisbane. The purpose of this thesis was to extend this anticancer vaccine technology by investigating whether the addition of a second co-stimulatory molecule, 4-1BBL, onto the surface of the vaccine cells could replace or reduce the requirement for DCs in the stimulation and activation of CD8+ T cells targeting the cancer cells.
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    Thesis Type
    Thesis (PhD Doctorate)
    Degree Program
    Doctor of Philosophy (PhD)
    School
    School of Medical Science
    DOI
    https://doi.org/10.25904/1912/3478
    Copyright Statement
    The author owns the copyright in this thesis, unless stated otherwise.
    Item Access Status
    Public
    Subject
    Melanoma
    T-cells
    CD8+ T cells
    Publication URI
    http://hdl.handle.net/10072/367230
    Collection
    • Theses - Higher Degree by Research

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