Terapija z modificiranimi celicami T z izraženim himernim receptorjem za tumorske antigene

Kern, Petra (author), Narat, Mojca (mentor)

CAR-T celična terapija je ena od novejših in uspešnejših metod za zdravljenje raka. Temelji na opremljanju pacientu avtolognih celic T z receptorji CAR, ki so sposobni prepoznati tumorske antigene in sprožiti odziv limfocitov T. Receptorji CAR so fuzijski proteini sestavljeni iz značilnih domen: vezavne domene, ekstracelularne povezovalne domene, transmembranske domene, signalizacijske domene in kostimulatorne domene. Vsaka od njih ima specifično funkcijo in vpliva na delovanje receptorja CAR in CAR-T celične terapije. Produkcija celic CAR-T poteka v več korakih. Najprej pacientu odvzamejo limfocite T, nato jih aktivirajo in transformirajo, jih razmnožijo in vrnejo v pacienta v obliki infuzije. Celice se nato še naprej razmnožujejo v pacientu in vršijo svojo funkcijo napadanja in uničevanja tumorskih celic. Kljub začetnim velikim uspehom terapije na področju zdravljenja levkemij, ima terapija svoje resne stranske učinke. Glavna problema terapije sta sindrom prekomernega izločanja citokinov in toksičnost zaradi napada na zdrave celice, ki izražajo tumorski antigen. Pojavljajo se mnoge rešitve teh problemov. Glavne so uporaba samomorilskih mehanizmov, pri katerih se celice CAR-T ob prisotnosti induktorja uničijo, in uporaba kombinacij receptorjev CAR z bolj specifično ločevanje tumorskih od zdravih celic.

• Language: Slovenian
• Keywords: biotehnologija, CAR-T, rak, imunoterapija, celična terapija, limfociti T
• Work type: Bachelor thesis/paper
• Typology: 2.11 - Undergraduate Thesis
• Organization: BF - Biotechnical Faculty
• Publisher: [P. Kern]
• Year: 2018
• PID: 20.500.12556/RUL-102605
• UDC: 60:616-006.4:615.37(043.2)
• COBISS.SI-ID: 9057913
• Publication date in RUL: 05.09.2018

KERN, Petra, 2018, Terapija z modificiranimi celicami T z izraženim himernim receptorjem za tumorske antigene [online]. Bachelor’s thesis. P. Kern. [Accessed 30 March 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=102605

Secondary language

• Language: English
• Title: Therapy with modified T-cells that express chimeric receptor for tumor antigens

Abstract

CAR-T cell therapy is one of the newest and most successful methods for treating cancer. The therapy is based on transducing CAR receptors into patient's autologous T cells. CAR receptors are fusion proteins capable of recognising tumour antigens and activating lymphocyte T response. CAR receptors comprise of five typical domains: antigen-binding domain, extracellular spacer, transmembrane domain, signaling domain and costimulatory domain. Each of them has a specific function and affects how the CAR receptor and CAR-T cell therapy performs. Production of CAR-T cells is done in multiple steps. First, patient’s allogenic lymphocytes T are taken from his blood, then they are activated and transformed with CAR receptor gene, expanded and returned into the patient’s blood in a form of an infusion. After the infusion, the cells continue to proliferate in the patient and perform their function of attacking and killing tumour cells. Alongside the initial big success of the therapy for leukemias, there are some severe side effects of the therapy that need to be addressed. The biggest issues are cytokine release syndrome and on-target off tumour toxicities. Various solutions for the problems have arisen. The main two strategies are the use of suicide mechanisms that induce apoptosis in CAR-T cells when inductor molecule is administered, and the use of a combination of CAR receptors that is capable of distinguishing between heathy and cancerous cells.

• Keywords: biotechnology, CAR-T, cancer, immunotherapy, cell therapy, lymphocytes T