Klinička imunoterapija tumora s antitijelima protiv inhibicijskih receptora T-limfocita

master's thesis

• Title (english): Clinical immunotherapy of tumors with monoclonal antibodies against checkpoint molecules on T-lymphocytes
• Author: Marko Mežnarić
• Mentor: Antonio Juretić (mentor)
• Committee member: Drago Batinić (predsjednik povjerenstva)
• Committee member: Nikola Đaković (član povjerenstva)
• Committee member: Antonio Juretić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Clinical Oncology); Zagreb
• Defense date and country: 2018-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology

Abstract

Incidencija malignih bolesti je u kontinuiranom porastu. Postoji više načina liječenja, a jedan od njih je imunoterapija. U ovom preglednom radu će se govoriti o jednoj od metoda imunoterapije koja koristi protutijela protiv molekula kontrolnih točaka T-limfocita. U obrani organizma od tumora, T-limfociti imaju važnu ulogu. Međutim, na njihovoj površini postoje autoregulacijske molekule koje sprječavaju prejaki imunosni odgovor kod, na primjer, autoimunosnih reakcija ali, s druge strane, takve molekule onemogućavaju puno djelovanje Tlimfocita protiv tumora. Cilj ovog preglednog rada je opisati način djelovanja te terapije, njene prednosti, uspjehe i nedostatke. U posljednjih nekoliko godina odobreno je od strane regulatornih agencija nekoliko monoklonskih protutijela protiv spomenutih molekula. To je bilo potaknuto uspjesima u pretkliničkim, a kasnije i kliničkim istraživanjima. Nakon odobrenja prvih protutijela za prve indikacije, došlo je do daljnjih odobrenja ili proširenja indikacija. Kod određenih slučajeva, ovakva se terapija može koristiti kao prva linija liječenja. Dosad se pokazalo da su nuspojave takve terapije razmjerno dobro podnošljive. Treba imati na umu da se radi o specifičnim nuspojavama, najčešće uzrokovanima djelovanjem imunosnog sustava. Jedan broj protutijela je trenutno u fazi kliničkih ispitivanja i očekuju se nova odobrenja kao i proširenja indikacija za korištenje dosadašnjih lijekova. ----- METODE: Pretraživane su elektroničke baze podataka PubMed i Uptodate.

Abstract (english)

The incidence of malignant diseases has been rising continuosly. There are several modes of cancer treatment and one of them is immunotherapy. This review will discuss one of the methods of immunotherapy where monoclonal antibodies are used against checkpoint molecules on T-lymphocytes. T-lymphocytes have an important role in tumor defense. However, on their surface regulatory molecules can be found that prevent an excessive immune response such as an autoimmune reaction. On the other hand, these molecules can prevent adequate antitumor activity of T-lyphocytes. The goal of this review is to describe the mechanism of action, benefits, achievements, and deficiencies of this type of therapy. In the last few years, regulatory agencies have approved the use of several antibodies against the mentioned molecules. This was encouraged by good results in preclinical and, later, clinical trials. After the approvals of the first antibodies for some indications, new antibodies were approved and the indications for their use were extended. In some cases, this therapy can be used as a first-line therapy. It has been shown so far that the side effects of this treatment were well tolerated. They can be specific and are mostly caused by this treatment's effect on the immune system. Several new antibodies are now being tested in clinical trials and we can expect new approvals and wider indications for the alredy approved drugs. ----- METHODS: electronic databases PubMed and Uptodate were searched.

• Keywords: blokada kontrolnih točaka; CTLA-4 antagonisti; PD-1 antagonisti; inhibicijske molekule na T-limfocitima; negativna povratna sprega T-limfocita
• Keywords (english): checkpoint blockade; CTLA-4 antagonists; PD-1 antagonists; inhibitory molecules on T-lymphocytes; negative feedback mechanism of T-lymphocytes
• Language: croatian
• URN:NBN: urn:nbn:hr:105:033070
• 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: 2019-01-08 09:02:11