20.500.12556/RUL-161200 Primerjava mehanizma delovanja celic CAR-T in zaviralcev imunskih kontrolnih točk Comparison of the Mechanism of Action of CAR-T Cells and Immune Checkpoint Inhibitors Zaviralci imunskih kontrolnih točk in celice CAR-T sta terapevtska pristopa, ki se lahko uporabljata za zdravljenje raka. Obe terapiji vplivata na delovanje limfocitov T, a imata popolnoma drugačen mehanizem delovanja. Na eni strani imamo celice T, modificirane s sintetičnim himernim antigenskim receptorjem (CAR), ki obstaja v petih različnih izvedbah. Na drugi strani pa imamo zaviralce imunskih kontrolnih točk, kjer se uporablja humanizirana monoklonska protitelesa. Celice CAR-T s himernim receptorjem same prepoznajo in vežejo antigene ter nato preko izločanja granzima in perforina, sinteze citokinov ali Fas/FasL poti uničijo rakave celice. Pri zaviralcih imunskih kontrolnih točk pa se protitelesa anti-CTLA-4 in anti-PD-1 vežejo na inhibitorne receptorje na celicah T in tako preprečijo interakcije receptorjev CTLA-4 in PD-1 z ligandi. S tem omogočijo vzpostavitev naravnih efektorskih funkcij in blažijo kronično utrujenost celic T, s tem pa tudi njihovo protirakavo delovanje. Tekom diplomske naloge bom najprej podrobneje predstavila receptorja CTLA-4 in PD-1 in njune zaviralce ter celice CAR-T, nato pa bom izpostavila še glavne razlike v mehanizmu delovanja med terapijama. Checkpoint inhibitors and CAR-T cells are therapeutic approaches that can be used to treat cancer. Both therapies affect the function of T lymphocytes, but they have completely different mechanisms of action. On one hand, there are T cells modified with a synthetic chimeric antigen receptor (CAR), which exists in five different versions. On the other hand, there are checkpoint inhibitors, which use humanized monoclonal antibodies. CAR-T cells with the chimeric receptor independently recognize and bind to antigens, and then destroy cancer cells through the secretion of granzyme and perforin, cytokine synthesis, or the Fas/FasL pathway. With checkpoint inhibitors, anti-CTLA-4 and anti-PD-1 antibodies bind to inhibitory receptors on T cells and thus prevent the interactions of CTLA-4 and PD-1 receptors with ligands. This enables the establishment of natural effector functions and alleviates chronic T cell fatigue, thereby enhancing their anti-cancer activity. In my thesis, I will first provide a detailed overview of the CTLA-4 and PD-1 receptors and their inhibitors, as well as CAR-T cells, and then highlight the main differences in the mechanisms of action between the two therapies. Celice CAR-T zaviralci imunskih kontrolnih točk mehanizem delovanja imunoterapija raka receptor CAR PD-1/PD-L1 CTLA-4 CAR-T cells immune checkpoint inhibitors mechanism of action cancer immunotherapy CAR-T receptor PD-1/PD-L1 CTLA-4 true false false Slovenski jezik Angleški jezik Diplomsko delo/naloga 2024-09-08 07:17:56 2024-09-08 07:17:59 2024-09-13 10:05:47 0000-00-00 00:00:00 2024 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 243858 207417603 41744.pdf 41744.pdf 1 01D13A483802A7D6AEEC1DCFFB78697F 2bb1a69a5def4c88a2b0d109d3628266301aa00bf04ea60ac0d476ec4078edd1 ae1dc166-6da1-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=190085 Biotehniška fakulteta 0 0 0