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Title: Modulation of T-cell responses to murine melanoma by targeted-cytokine therapy
Author: Becker, Jürgen C.
ISNI:       0000 0001 3453 3292
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2001
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The present thesis describes the characterization of T cell responses to melanoma and its modulation by in situ cytokine therapy. Previous studies have shown that antibody cytokine fusion proteins, designated immunocytokines, achieve high cytokine concentrations in the tumor microenvironment and thereby effectively stimulate cellular immune responses against malignancies. Analysis of the T cell receptor repertoire of tumor infiltrating lymphocytes, as presented here, revealed operative differences in the immunomodulatory capacity of two proinflammatory cytokines, i.e., interleukin 2 and lymphotoxin ɑ, if applied targeted to the tumor site. While interleukin 2 is boosting an already established T cell response and enables the recirculation of clonally expanded T cells, lymphotoxin ɑ's modus operandi is relying on newly recruited T cells. Via induction of a tertiary lymphoid organ at the tumor site lymphotoxin a immunocytokines allow the recruitment, priming, and activation of naïve T cells to harness an effective T cell response against the tumor.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Immunology; Melanoma; Immuno-cytokines