Eradication of established murine mesothelioma tumours by combined immunotherapy

Shruti Krishnan

    Research output: ThesisDoctoral Thesis

    373 Downloads (Pure)

    Abstract

    [Truncated] Despite the recent progress made in applying immunotherapy for the treatment of various cancers, such a therapy has not been developed for treating mesothelioma. Mesothelioma has a latency period of 30-40 years with a median survival being 9-10 months from diagnosis. Due to the lack of early diagnostic capabilities, patients in general, present with well-advanced disease that renders many therapeutic options ineffective. Standard treatments for the management of mesothelioma are limited due to late diagnoses, significant toxicities and the occurrences of relapses. Targeted therapies such as immunotherapy are selective and are aimed at stimulating the host’s immune system to produce complete tumour destruction. The work described in this thesis, and the work of others in both mouse tumour models and clinical settings has shown that simultaneous targeting of multiple immune mechanisms results in better outcomes.
    A major deterrent to boosting anti-tumour immune activity was the immunosuppressive environment within the growing tumours themselves. Work carried out by our laboratory, and others, defined the role of Tregs and TGF-β in suppressing immune responses to growing tumours. This led to the hypothesis that overcoming immune suppression alone was not sufficient, and perhaps an additional boost to effector T cell activity would improve the outcome.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2015

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