Modulation of T-cell responses to Murine Melanoma by Targeted-Cytokine Therapy.

Becker, Jürgen C. (2001). Modulation of T-cell responses to Murine Melanoma by Targeted-Cytokine Therapy. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f998

Abstract

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.