The generation of cytotoxic T cell epitopes and their generation for cancer immunotherapy

Kessler, J. (2009)

Doctoral Thesis

Cytotoxic T cell epitopes are the targets for a T cell mediated immunotherapy of cancer. The thesis reports on their identification in the tumor associated proteins BCR-ABL and PRAME by the reverse immunology (prediction) strategy. An extended strategy is used, including the analysis of the C-terminal generation of potential epitopes by the proteasome. Novel HLA class I peptide binding assays were developed to enable further epitope discovery. Fundamental studies were performed to identify novel non-proteasomal cytosolic endopeptidases in the HLA class I antigen processing pathway. Nardilysin and thimet oligopeptidase were identified to generate in a concerted action an HLA-A3 restricted CTL epitope from PRAME. The general roles of nardilysin and TOP in class I processing were investigated.

• Cancer
• Cytotoxic T cell epitope
• Epitope
• HLA class I
• HLA class I peptide binding
• MHC class I
• Nardilysin
• Proteasome
• Thimet oligopeptidase

• All authors: Kessler, J.
• Supervisor: Melief, C.J.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2009-10-27