Several tumour-associated antigens have been used safely in clinical trials of therapeutic anti-cancer vaccination with modest clinical outcomes. This inability to stimulate an effective anti-tumour response could be due to the poor choice of antigens used for vaccination, necessitating an improvement and broadening of antigenic selection for cancer immunotherapy.
The over-expressed tumour-associated antigens Survivin and telomerase reverse transcriptase (TRT), are attractive because they are ubiquitously ex pressed and are required for maintenance of cancer cell growth. The immune responses against these antigens will be characterised in patients with non-small cell lung carcinoma (NSCLC). Emphasis will be given to the underlying T cell response to establish whether it is of a reasonable magnitude and/or of sufficient and broad epitope specificity to overcome tumour clones that escape immune surveillance.
The specific aims will address the following: Do patients with NSCLC exhibit tumour-induced T cell responses against particular or multiple T cell epitopes present in Survivin and TRT? Does this response vary in frequency and specificity from that seen in normals? Does disease progression relate to T cell epitope spreading involving multiple HLA geno-types? Does the in situ, quantifiable detection of these antigens on tumour specimens predict disease severity?
In addressing these aims, it will be determined whether these antigens can be used as immunotherapeutic agents in NSCLC. Cancer immunotherapy directed against multiple epitopes of tumour-associated antigens may be beneficial in a broad range of cancer patients. This fellowship will enable me to become established as a scientist in a highly respected medical research institute in Greece. I will train in a stimulating environment that can only benefit my scientific aspirations. This will be a stepping- stone for my future academic career within the Hellenic and European Medical Research establishment.
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