KLINIČKA IMUNOTERAPIJA RAKA BLOKADOM MOLEKULARNIH INTERAKCIJA NEGATIVNE POVRATNE SPREGE

Antonio Juretić, Martina Bašić-Koretić

Nedavni uspješni rezultati više raznih novih imunoterapijskih pristupa u onkoloških bolesnika, kao, primjerice, blokada imunosnih inhibitornih molekularnih interakcija s monoklonskim protutijelima protiv molekula kontrolnih točaka, mogu se smatrati medicinskim iskorakom u kliničkoj onkologiji. Cilj je ovoga rada dati pojednostavnjeni prikaz imunosnog uređivanja raka i kliničke primjene monoklonskih protutijela protiv molekula kontrolnih točaka u onkoloških bolesnika. Interakcije između imunosnog sustava i autolognih tumora složene su, ali rezultati dobiveni primjenom monoklonskih protutijela protiv molekula kontrolnih točaka upućuju na prihvatljivu kliničku primjenjivost, učinkovitost i sigurnost u liječenju bolesnika s određenim tipovima raka. Klinička primjena monoklonskih protutijela protiv molekula kontrolnih točaka CTLA-4, PD-1 i PD-L1, ovisno o tome protiv kojih se tumora ta protutijela testiraju i primjenjuju, jest u rasponu od odobrenja regulatornih agencija i primjene u metastatskoj bolesti u bolesnika s određenim vrstama tumora pa do faza testiranja u kliničkim studijama, a radi istraživanja kliničke učinkovitosti i dobivanja odobrenja.

The recent successful results of several relatively new immunotherapeutic anti-cancer strategies such as the blockade of immune inhibitory pathways by monoclonal antibodies against checkpoint molecules can be considered as a medical breakthrough in clinical cancer immunotherapy. This paper presents a basic overview of cancer immunoediting and the clinical application of monoclonal antibodies against checkpoint molecules in cancer patients. Interactions between the immune system and the malignancy are complex, but the results obtained by using the above mentioned therapeutic approaches indicate acceptable clinical utility, efficacy and safety against several types of cancer. Clinical application of monoclonal antibodies against checkpoint molecules CTLA-4, PD-1, and PD-L1, depending on which tumors these antibodies are tested and applied against, ranges from their already usage having been approved by regulatory agencies for patients with particular metastatic tumors to their testing in clinical studies with the aim of demonstrating their efficiency and consequently obtaining approval.