20.500.12556/RUL-109163 Pomen zaviralcev kontrolnih točk pri razvoju novih terapevtskih pristopov zdravljenja raka The role of checkpoint inhibitors in the development of new therapeutic approaches for cancer treatment Imunoterapija raka je oblika terapije, ki uporablja različne snovi za spodbujanje, izboljšanje ali obnovo delovanja pacientovega imunskega sistema pri prepoznavanju in eliminaciji tumorskih celic. Zaviralci kontrolni točk veljajo za najobetavnejše imunoterapevtike do zdaj. Gre za monoklonska protitelesa ali fuzijske proteine, ki se specifično vežejo na kontrolne točke imunskega sistema. Lahko so tudi v obliki molekul, ki z vezavo na encim inhibirajo njegovo aktivnost. S tem se spremenijo signalne poti, ki regulirajo imunski sistem in njegov odziv. Najbolj raziskani kontrolni točki sta CTLA-4 in os PD-1/PD-L1. Obe zavirata celično posredovani imunski odziv, zlasti limfocite T. CTLA-4 regulira obseg aktivacije limfocitov T v zgodnjih fazah imunskega odziva, medtem ko os PD-1/PD-L1 ustavlja imunski odziv v poznih efektorskih fazah. Na osnovi omenjenih kontrolnih točk se v klinični praksi uporablja 7 različnih zaviralcev kontrolnih točk za številne oblike rakavih obolenj. Zaradi visoke učinkovitosti, dolgotrajnega odziva in nizke toksičnosti teh imunoterapevtikov se intenzivno raziskujejo nove kontrolne točke, kot so LAG-3, IDO-encim, TIM-3, ICOS, 4-1BB, OX40, CD27, GITR in CD40. Hkrati pa se zaviralci kontrolnih točk testirajo tudi v kombinaciji z že znanimi terapijami raka. Cancer immunotherapy employs different strategies to stimulate, improve or reactivate the patient’s immune system to destroy cancer cells. There are several types of immunotherapy amongst which immune checkpoint inhibitors are the most promising. Immune checkpoints refer to a plethora of signalling pathways that regulate the immune response. Therefore, many of the immune checkpoint inhibitors are based on monoclonal antibodies or fusion proteins that bind to immune checkpoints. In some cases, they can also be based on molecules that bind to immune-inhibitory enzymes and deactivates them. The utilization of the immune checkpoint inhibitors shifts the signalling pathways responsible for regulating the immune response. CTLA-4 and PD-1/PD-L1 axis are the most researched immune checkpoints, with inhibitory effects on the cell-mediated immune response. CTLA-4 downregulates the activation of T cells in the early stages of the immune response, while the PD-1/PD-L1 axis downregulates the effector phase of the immune response. There are 7 different FDA approved immune checkpoint inhibitors to treat many different types of cancer. Due to their durable responses in a significant percentage of cancer patients and low toxicity new immune checkpoints such as LAG-3, IDO-enzyme, TIM-3, ICOS, 4-1BB, OX40, CD27, GITR, and CD4 are being extensively researched. At the same time, researchers are testing existing immune checkpoints in combination with other cancer therapies. zaviralci kontrolnih točk imunoterapija rak kontrolne točke PD-1 CTLA-4 checkpoint inhibitors immunotherapy cancer checkpoints PD-1 CTLA-4 true false false [T. Klenovšek] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2019-08-24 07:45:03 2019-08-24 07:45:08 2022-08-21 03:40:22 0000-00-00 00:00:00 2019 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 606:616-006.6:577.27:615.37(043.2) 166347 9282425 7501.pdf 7501.pdf 1 9042AAB57EDFA630766EA5A95CB0A51F 11d6c11254174e542654206003b4e8f7c93b9977cfe395e6ef0e673b165b9fa0 cb46f5e7-a1b6-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=120654 Biotehniška fakulteta 0 0 0