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Premagovanje neželenih učinkov povezanih s celično terapijo CAR-T
ID Pleško, Ema (Author), ID Jerala, Roman (Mentor) More about this mentor... This link opens in a new window

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Abstract
CAR-T celična terapija je učinkovita metoda za zdravljenje raka. CAR receptorski proteini dajo limfocitu T, v katerega so vneseni sposobnost vezave na specifičen antigen, ki ga na svoji površini izražajo rakave celice. CAR receptorji so zgrajeni iz več domen, ki omogočajo učinkovito aktivacijo in proliferacijo CAR T celic. Zaradi nevarnosti terapije kot je prekomerna produkcija citokinov in aktivacija CAR T celic v zdravem tkivu prihaja do neželenih učinkov. Najpogostejša med njimi sta sindrom sproščanja citokinov in nevrotoksičnost, ki v nekaterih primerih povzročita smrt pacientov. Obstaja nekaj zdravilnih učinkovin za lajšanje simptomov, a je zaradi nepopolnega poznavanja patogeneze bolezni njihova uporaba omejena. Pojavljajo se različne modifikacije CAR receptorjev in druge metode, ki bi preprečile sam nastanek neželenih učinkov ali v primeru hujših neželenih učinkov ustavile delovanje CAR T celic in s tem nadaljnji razvoj bolezni. Glavni rešitvi sta sistem samomorilskih genov, ki ob prisotnosti induktorja CAR T celice uničijo in tarčna aktivacija, ki zajema mehanizme kombinacije istočasnega prepoznavanja dveh tumorskih antigenov, aktiviranja preko stikala in aktivacije CAR T celic z induktorjem. Mehanizmi tarčne aktivacije temeljijo predvsem na bolj specifičnem ločevanju tumorskih celic od zdravega tkiva. Poleg teh so v fazah raziskav še druge metode, ki se kažejo kot obetavne.

Language:Slovenian
Keywords:biotehnologija, imunoterapija, rak, levkemija, CAR-T, sindrom sproščanja citokinov, nevrotoksičnost
Work type:Bachelor thesis/paper
Typology:2.11 - Undergraduate Thesis
Organization:BF - Biotechnical Faculty
Publisher:[E. Pleško]
Year:2020
PID:20.500.12556/RUL-117311 This link opens in a new window
UDC:606:61.155.392:602.68(043.2)
COBISS.SI-ID:21981443 This link opens in a new window
Publication date in RUL:05.07.2020
Views:2651
Downloads:390
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Secondary language

Language:English
Title:Overcoming toxicities associated with CAR-T cell therapy
Abstract:
CAR-T cell therapy is an effective method for treating cancer. CAR receptor proteins give T lymphocyte the ability to bind to a specific antigen which is expressed on the surface of cancer cells. CAR receptors are constructed from multiple domains that allow efficient activation and proliferation of CAR T cells. However toxic side effects do occur due to excessive cytokine production and CAR T cell activation in healthy tissue. The most common and threatening side effects are cytokine release syndrome and neurotoxicity, which in some cases result in death. There are some drugs avaliable to relieve symptoms, but due to incomplete knowledge of the pathogenesis of diseases, their use is limited. Various modifications of CAR receptors and other methods are emerging that would prevent the occurrence of side effects or, in the case of severe side effects, stop the functioning of CAR T cells and thus further development of the disease. Currently the main solutions are suicidal genes that destroy CAR T cells in the presence of an inducer and target activation, which includes targeting two tumor-associated antigens, switch-mediated activation and activation of CAR T cells by an inducer. The mechanisms of target activation are based primarily on a more specific separation between tumor cells and healthy tissue. In addition to these, there are other methods in the research phases which appear promising.

Keywords:biotechnology, immunotherapy, cancer, leukemia, CAR-T, cytokine release syndrome, neurotoxicity

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