Adoptivní transfer tumor-specifických lymfocytů v imunoterapii nádorových onemocnění

• Název práce v češtině: Adoptivní transfer tumor-specifických lymfocytů v imunoterapii nádorových onemocnění
• Název v anglickém jazyce: Adoptive transfer of tumor-specific lymphocytes for cancer immunotherapy
• Klíčová slova: adoptivní T buněčný transfer, DCVAC/PCa, karcinom prostaty, protinádorová imunoterapie
• Klíčová slova anglicky: adoptive T cell transfer, DCVAC/PCa, prostate cancer, antitumor immunotherapy
• Akademický rok vypsání: 2013/2014
• Typ práce: disertační práce
• Jazyk práce: čeština
• Ústav: Ústav imunologie (13-722)
• Vedoucí / školitel: prof. MUDr. Jiřina Bartůňková, DrSc.
• Řešitel: skrytý - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 05.08.2014
• Datum zadání: 05.08.2014
• Datum potvrzení stud. oddělením: 05.08.2014
• Datum a čas obhajoby: 04.09.2020 08:00
• Datum odevzdání elektronické podoby: 01.04.2020
• Datum odevzdání tištěné podoby: 01.04.2020
• Datum proběhlé obhajoby: 04.09.2020
• Oponenti: RNDr. Šárka Němečková, DrSc.

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Předběžná náplň práce

Karcinom prostaty je druhou nejčastější příčinou úmrtí mužů na rakovinu v Evropě a USA. V kontextu dosavadních preklinických experimentů a klinických studií existují předpoklady pro úspěšné uplatnění imunoterapie v jeho léčbě. Slibných výsledků je dosaženo převážně kombinací různých léčebných modalit, kdy dochází k jejich synergickému protinádorovému působení. Jednou z možností je využití protinádorových vakcín a adoptivního T buněčného transferu.
Téma této dizertační práce navazuje na dlouhodobý výzkumný program pracoviště kandidátky v oblasti protinádorové imunoterapie. Obecná část dizertační práce podává základní přehled o mechanismech protinádorové imunity a o roli jednotlivých složek imunitního systému při jejím zajištění. Další části se věnují současným imunoterapeutickým přístupům s důrazem na metodu adoptivního T buněčného transferu a jejího uplatnění v léčbě karcinomu prostaty. Ve vlastní výzkumné části předkládá vypracovaný experimentální protokol pro adoptivní transfer tumor specifických T lymfocytů, a dále protokol zabývající se ex vivo obohacením buněčných populací o peptid-specifické T lymfocyty u pacientů s karcinomem prostaty. V rámci našeho výzkumu uvádíme též výsledky klinické studie, která si kladla za cíl ověřit biologickou bezpečnost, schopnost indukce imunitní protinádorové odpovědi a zhodnotit klinické odpovědi pacientů na imunoterapeutický léčivý přípravek na bázi dendritických buněk s označením DCVAC/PCa

Předběžná náplň práce v anglickém jazyce

Prostate cancer is the second leading cause of cancer death in men in Europe and the US. In the context of previous preclinical experiments and clinical studies there are certain assumptions predicating successful application of immunotherapy in the treatment of patients with prostate cancer. Promising results have been achieved by a combination of different treatment modalities which provide a synergistic antitumor effect. One of these combinatorial options is the use of antitumor vaccines and adoptive T cell transfer.
The topic of this thesis is to provide a fresh insight into the past and current trends following the long-term candidate´s department program in the field of anti-tumor immunotherapy. The experimental part of this thesis revolves around our own results published in this field. The introductory chapter delivers a basic overview of cellular mechanisms of anti-tumor immunity and the role of individual immune components in these processes. Following chapters are dedicated to current immunotherapeutic approaches with emphasis on the adoptive T cell transfer and implication of this technology in the treatment of prostate cancer. The results section describes the establishment of our protocol for adoptive T cell transfer as well as the protocol for ex vivo enrichment of human T cell populations for cancer peptide-reactive T lymphocytes in patients with prostate cancer. Importantly, this thesis also includes our clinical data aimed at testing the biosafety of established protocol, evaluation of the capacity of patients T cells to induce anti-tumor immune responses as well as the assessment of the patient’s clinical responses to a DCVAC/PCa dendritic cell-based vaccine.