Imunoterapija karcinoma pluća

master's thesis

• Title (english): Lung cancer immunotherapy
• Author: Lucija Dželalija
• Mentor: Marko Jakopović (mentor)
• Committee member: Mateja Janković Makek (predsjednik povjerenstva)
• Committee member: Miroslav Samaržija (član povjerenstva)
• Committee member: Marko Jakopović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2021-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology

Abstract

Karcinom pluća jedna je od vodećih nezaraznih bolesti u svijetu. Glavni je uzrok smrti od karcinoma i procjenjuje se da od nje godišnje umre oko 1 500 000 ljudi. Nastanak karcinoma je uglavnom povezan s pušenjem. Glavni problem ove bolesti je kasno postavljena dijagnoza. Klasična kemoterapija i radioterapija nisu davale željene rezultate u liječenju uznapredovale faze bolesti. One relativno kratko produžuju život oboljelog i ne nude potencijalno zaliječenje i izlječenje. Saznanje da imunološki sustav igra veliku ulogu u kancerogenezi otvara nove opcije u liječenju karcinoma. Ideja ove terapije je poticanje protutumorskih mehanizama i direktno utjecanje na inhibiciju rasta. Imunoterapija se temelji na manipulaciji protutijelima, imunološkim stanicama i ključnim receptorima. Razvijena su i cjepiva koja nisu pokazala zadovoljavajuću učinkovitost. Blokatori kontrolnih točaka pokazuju dobru učinkovitost u liječenju bolesnika s karcinomom pluća koji su ranije liječeni klasičnom kemoterapijom. Adoptivna stanična terapija prikuplja imunološke stanice iz perifrne krvi ili samoga tumora i ex vivo vrši ekspanziju linija specifičnih za tumor. Novija istraživanja genetičkog inženjeringa usmjerena su stvaranju kimeričkih antigenskih receptora (CAR) na površini T-stanica. Prednost sintetički stvorenog CAR-a je u tome jest sposobnost premošćivanja MHC molekule suprimirane od strane tumora. Provode se istraživanja s ciljem razvoja tumorskih biomarkera koji bi se mogli koristiti u procjeni učinkovitosti terapije i kao prediktivni čimbenici. Imunoterapija ima i neka ograničenja kao što su adekvatan odabir pacijenata, autoimuna toksičnost i visoka cijena. Nova saznanja iz područja imunoonkologije i novootkrivene molekularne značajke samog tumora podloga su za usavršavanje postojećih lijekova i traganje za novima.

Abstract (english)

Lung cancer is one of the leading non-infectious diseases in the world. It is the leading cause of death from malignancies with more than 1 500 000 deaths. The onset of lung cancer is mainly related to smoking. The main problem of this disease is its late diagnosis. Classical chemotherapy and radiotherapy didn't give expected resaults in treatement of progressive disease. They prolong a patient's life for a relatively short amount of time and do not offer complete healing. The knowledge that the immune system plays a major role in cancerogenesis opens up new possibilities for cancer treatement. The idea behind this therapy is to stimulate the antitumor mechanisms and direct inhibition of tumor's growth. The principles of immunotherapy are mostly based on the manipultion of antybodies, immune cells and key receptors. The anti-tumor vaccines have been developed, but they didn't show effective resaults. Checkpoint blockers have shown good efficiency in the treatement of patients with lung cancer previously treated with classic chemotherapy. Adoptive cell therapy collects immune cells from peripheral blood or the tumor itself and expand the tumor specific cell line ex-vivo. Recent genetic engineering research has focused on the creation of chimeric antigen receptors (CARs) on the surface of T-cells. The advantage of a synthetically created CARs is its abillity to bypass the tumor-supressed MHC molecule. The main goal of research is developement of tumor biomarkers that could be used in evaluation of therapy efficiency and as predictive factors. Immunotherapy has some limitations such as adequate selection of patients, autoimmune toxicity and high price. New insights in field of immunooncology and newly discovered molecular features of the tumor have set the groundwork for perfecting the existing and seeking for the new treatement.

• Keywords: karcinom pluća; imunoterapija; antitijelo; inhibitor kontrolne točke; biomarker
• Keywords (english): lung carcinoma; immunotherapy; antibody; checkpoint inhibitor; biomarker
• Language: croatian
• URN:NBN: urn:nbn:hr:105:132307
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-02-03 09:20:41