Active immunotherapy of cancer: An overview of therapeutic vaccines

Abstract

Cancer is one of the leading causes of morbidity and mortality worldwide and great efforts are underway to develop new therapeutic protocols. One of the approaches is immunotherapy which uses the immune system and its components to fight against cancer. The two main axes of cancer immunotherapy refer to passive and active treatments. Passive immunotherapy includes administration of tumor-specific antibodies and autologous T cells which destroy tumor cells, while active immunotherapy is directed at inducing the patient´s own antitumor immune responses and refers to cancer vaccines and immune checkpoint inhibitors. Vaccination of tumor-bearing individuals with tumor cells/antigens or autologous dendritic cells pulsed with tumor antigens may result in enhanced antitumor immune response. However, vaccine design is a complex, multi-component task, and the optimal combinations of antigens, adjuvants, delivery methods and routes of administration need to be precisely defined. Active immunotherapy also addresses the immunosuppressive and tolerogenic mechanisms developed by tumors. This review provides an overview of new results from clinical studies of therapeutic cancer vaccines and discusses their implications for the clinical use, alone or in combination with other immunotherapeutic strategies.

Maligni tumor (rak, karcinom) je jedan od vodećih uzroka obolevanja i smrtnosti pa se veliki napori ulažu u razvoj novih terapijskih pristupa. Savremena imunoterapija malignih tumora obuhvata primenu antitumorskih antitela i autologih T ćelija koje uništavaju ćelije tumora (pasivna imunoterapija) i pojačanje slabog antitumorskog imunskog odgovora domaćina (aktivna imunoterapija) vakcinacijom i primenom antitela koja blokiraju inhibitorne receptore (kontrolne tačke) T limfocita. Vakcinacija pacijenata obolelih od tumora njihovim sopstvenim tumorskim ćelijama, antigenima tih ćelija ili dendritskim ćelijama koje su inkubirane sa tumorskim antigenima stimuliše imunski sistem pacijenta da prepozna tumorske antigene i eliminiše maligne ćelije. Međutim, razvoj terapijskih tumorskih vakcina suočen je sa brojnim izazovima vezanim za njihov dizajn, u smislu optimalne kombinacije antigena, adjuvansa i nosača, kao i za način primene. Pored toga, savremena aktivna imunoterapija treba da prevaziđe nisku imunogenost tumora i imunosupresivne mehanizme mikrosredine tumora kod pacijenata sa klinički ispoljenom bolesti. U ovom radu prikazani su rezultati novijih kliničkih studija u kojima su ispitivane različite terapijske vakcine za karcinom i diskutovano je o njihovoj mogućoj primeni u kliničkoj praksi, kako samih, tako i u kombinaciji sa drugim imunoterapijama.