diplomsko delo
Tinkara Kreft (Author), Jernej Ogorevc (Mentor), Jernej Ogorevc (Thesis defence commission member), Mojca Narat (Thesis defence commission member), Jana Murovec (Thesis defence commission member)

Abstract

Terapija z modificiranimi limfociti T (CAR-T) je ena najsodobnejših oblik imunoterapije za zdravljenja raka. Temelji na genetsko spremenjenih, pacientu avtolognih celicah T, ki na svoji površini izražajo himerni antigenski receptor (ang. chimeric antigen receptor ali CAR). Ta je sposoben prepoznati tumorske antigene in sprožiti imunski odziv preko limfocitov T. Terapija s celicami CAR-T trenutno omogoča zdravljenje nekaterih oblik levkemij. Širšo uporabo omejuje zapleten in drag proces priprave celic CAR-T, majhno število znanih tumor-specifičnih antigenov, proti katerim bi usmerili delovanje CAR, slabo protitumorsko delovanje in preživetje celic CAR-T v toksičnem tumorskem mikrookolju ter neželeni stranski učinki terapije. Ena izmed strategij premagovanja omenjenih ovir je uporaba tehnik za preurejanje genoma na celicah CAR-T. Preko vodenih nukleaz, kot so ZFN, TALEN in CRISPR/Cas, lahko v genomu celic T ustvarimo mestno-specifične dvoverižne prelome DNA, ki aktivirajo popravljalne mehanizme. Te izkoriščamo za ustvarjanje želenih modifikacij v genomu celic CAR-T, kar bi lahko v prihodnosti omogočalo učinkovitejše in varnejše terapije. Trenutne strategije za razvoj učinkovitejših CAR-T terapij z uporabo genomskega preurejanja se usmerjajo predvsem v pripravo alogenih celic CAR-T, saj bi tako poenostavili proizvodnjo in naredili terapijo cenovno dostopnejšo. Cilj je tudi identifikacija dodatnih tumor-specifičnih antigenov, ki bi omogočili izboljšanje specifičnosti delovanja terapij CAR-T, in razvoj celic CAR-T, ki bi sposobnost proliferacije ohranjale tudi in vivo. V prihodnosti lahko pričakujemo nove celične terapije CAR-T, ki ne bodo le varnejše in učinkovitejše, temveč bodo omogočale tudi zdravljenje širšega spektra obolenj.

Keywords

CAR-T;preurejanje genoma;imunoterapija;rak;CRISPR/Cas;celična terapija;

Data

Language: Slovenian
Year of publishing:
Typology: 2.11 - Undergraduate Thesis
Organization: UL BF - Biotechnical Faculty
Publisher: [T. Kreft]
UDC: 606:616-006.6:602.68(043.2)
COBISS: 27445251 Link will open in a new window
Views: 591
Downloads: 152
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Other data

Secondary language: English
Secondary title: Application of genome editing technologies in development of more effective CAR-T
Secondary abstract: Therapy with modified T lymphocytes (CAR-T) is one of the most modern forms of immunotherapy for cancer treatment. It is based on genetically modified, autologous T cells, which express a chimeric antigen receptor (CAR) on their surface. This receptor is able to recognize tumor antigens and trigger a T lymphocytes - mediated immune response. CAR-T cell therapy currently enables treatment of some forms of leukemia. Extensive use is limited by the complex and expensive process of making CAR-T cells, lack of known tumour target antigens, poor antitumor efficacy and survival of CAR-T cells in a toxic tumor microenvironment, and side effects of the therapy. One of the strategies to overcome these barriers is the use of genome editing on CAR-T cells. Guided nucleases such as ZFN, TALEN and the CRISPR/Cas system introduce site-specific DNA double-strand breaks in the T cell genome, activating repair mechanisms, which are used to create desired modifications of the genome. Genome edited CAR-T cells may result in more effective and safer therapies in the future. Current strategies are primarily focused on the development of allogeneic CAR-T cells, as this would simplify production and make therapy more affordable. The aim is also to identify additional tumor-specific target antigens and develop CAR-T cells with better antitumor efficacy that would maintain the ability to proliferate in vivo. In the future, we can expect new CAR-T cell therapies, which will not only be safer and more effective, but will also enable the treatment of a wider range of diseases.
Secondary keywords: genome editing;immunotherapy;cancer;cell therapy;
Type (COBISS): Bachelor thesis/paper
Study programme: 0
Thesis comment: Univ. v Ljubljani, Biotehniška fak., Študij biotehnologije
Pages: VI, 20 str.
ID: 12006079