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Antigenome defines a selection of mutated tumor peptides driving tumor-specific T-cell response
Hadlová, Petra ; Drbal, Karel (advisor) ; Dibus, Michal (referee)
T cells, as an essential part of the adaptive immune system, play crucial role in eradication of tumor growth. T cells target, interact with and eventually annihilate the tumor cells in antigen- specific (Ag) manner. T cells interact with tumor cells via short epitopes bound to the major histocompatibility complex (MHC) molecules on the tumor cell surface. Tumor specific neoepitopes arise from random somatic mutations and constitute a part of the tumor antigenome. Antigenome comprises of two classes of antigens, tumor specific antigens (TSA) and tumor associated antigens (TAA). TSA are neoantigens carrying neoepitopes unique to each tumor. TAA are self-antigens presented by both tumor cells and non-transformed cells. Each tumor cell is able to develop numerous ways to evade the immune system consisting of T cells, NK cells, macrophages and other mechanisms employed. Despite that immunotherapy has shown a great potential in personalized medicine. The stratification of responsive patients is essential for effective and durable management of therapy in clinical practice. Methods are employed, which study existing reactive T cell clones, somatic mutations present in each patient, role of somatic mutations in tumor development and present neoepitopes. All these patient- specific features facilitate...
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Cytometric assay of antigen-specific T cell response in monitoring of BCG vaccine therapy
Hadlová, Petra ; Drbal, Karel (advisor) ; Kalina, Tomáš (referee)
Bladder carcinoma (BCa) is among the most common carcinomas in the Western world. Despite the availability of effective therapies, there is currently an urgent need to develop a stratification method, which would enable the accurate identification of patients responsive to therapy. In the theoretical part of my diploma project I describe the heterogeneity of BCa and the currently applied immunotherapeutic approaches. I specifically focused on the Bacillus Calmette-Guérin (BCG) vaccine instillation. For decades another use of BCG has been a prophylactic vaccination against tuberculosis (TB) infection. BCG serves as a model treatment because it is highly efficient when prescribed to the responsive patient. However, an effective stratification is yet to be developed for BCa and latent tuberculosis infection (LTBI) diagnosis and/or monitoring. In the experimental part of my project, I developed and tested a 10-parameter panel for T cell- specific activation test (TAT) applicable for a stratification of BCa patients as well as for the detection of LTBI. I tested the panel on positive controls using flow cytometry (FCM) method because it allows for detection and measurement of dozens of markers at a single cell level. It is easily applicable to available urine and blood samples obtained from BCa...
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Antigenome defines a selection of mutated tumor peptides driving tumor-specific T-cell response
Hadlová, Petra ; Drbal, Karel (advisor) ; Dibus, Michal (referee)
T cells, as an essential part of the adaptive immune system, play crucial role in eradication of tumor growth. T cells target, interact with and eventually annihilate the tumor cells in antigen- specific (Ag) manner. T cells interact with tumor cells via short epitopes bound to the major histocompatibility complex (MHC) molecules on the tumor cell surface. Tumor specific neoepitopes arise from random somatic mutations and constitute a part of the tumor antigenome. Antigenome comprises of two classes of antigens, tumor specific antigens (TSA) and tumor associated antigens (TAA). TSA are neoantigens carrying neoepitopes unique to each tumor. TAA are self-antigens presented by both tumor cells and non-transformed cells. Each tumor cell is able to develop numerous ways to evade the immune system consisting of T cells, NK cells, macrophages and other mechanisms employed. Despite that immunotherapy has shown a great potential in personalized medicine. The stratification of responsive patients is essential for effective and durable management of therapy in clinical practice. Methods are employed, which study existing reactive T cell clones, somatic mutations present in each patient, role of somatic mutations in tumor development and present neoepitopes. All these patient- specific features facilitate...
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Subpopulations of lymphocytes in patients with prostate cancer during the immunotherapy by dendritic cell vaccine
Volmová, Martina ; Lašťovička, Jan (advisor) ; Palich Fučíková, Jitka (referee)
The bachelor thesis looks into the issue of cancer immunotherapy and it deals with possible use of immunotherapy by dendritic cell vaccine in patients with prostate cancer, which is now in phase I/II of clinical trials on the Department of Immunology at Faculty hospital Motol. The target of the practical part was to cope with the technology of preparation of blood samples and their measurement by means of the flow cytometry, with subsequent data evaluation and processing. The highlight of this work was the statistical evaluation of obtained data of lymphocyte subpopulations levels in peripheral blood, and their possible correlation with disease progression. The main subject of the research were subpopulations CD3 +, CD4 +, CD8+ , CD16+ , CD19+ and HLA-DR+. The monitoring of these subpopulations in patients treated by dendritic cell vaccine showed the decrease of both leukocyte and lymphocyte levels, reduction of CD4/CD8 index, decrease of relative and absolute numbers of CD4+ cells and significant decrease of both relative and absolute B lymphocyte numbers during the progress of the disease. Powered by TCPDF (www.tcpdf.org)
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