טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentDassau Lior
SubjectIdentification of Peptides Antigens for Immunotherapy
of Small Cell Lung Carcinoma
DepartmentDepartment of Biology
Supervisor Professor Arie Admon


Abstract

Small cell lung cancer (SCLC) is an aggressive form of lung cancer, prevalent among smokers. Though, it response to chemotherapy initially, most of the patients relapse and cure is rare. SCLC originates from neuroendocrine cells and expresses neuronal markers. This research aims at identification of new SCLC specific HLA peptides potentially useful for immunotherapy and pointing to defectively rapid degradation of cellular proteins.

            The HLA peptides were identified by transfection of SCLC cell lines with vectors coding the HLA gene missing its transmembrane domain, resulting in expression of soluble HLA molecules, recovered in large amounts from the cell growth medium and purified by immunoaffinity. The peptides were resolved by nano-capillary reversed-phase HPLC and tandem mass spectrometry and identified using the new (Pep-Miner) software tool.

            The identified HLA peptides originated form known proteins, cancer related proteins, cell cycle regulatory proteins and even from a number of novel, yet un-characterized proteins. To evaluate their potential as candidates for immunotherapy, we have cloned the genes of the proteins involved with carcinogenesis, tumor growth, cell cycle or embryonic development of the neuronal system. Some of the studied genes contained disabling mutations.

            The studied gene products are being tested for their immunogenic potential by eliciting T-cells activation and serological response with cancer patient's lymphocytes and serum, respectively. The new approach of direct biochemical analysis of cancer peptides recovered from soluble HLA is demonstrated here at a promising approach for large scale identifications of new tumor antigens and studying the malfunction of the cells that lead to the carcinogenic transformation.