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Frank, Mojca; Ihan, Alojz (2006)
Publisher: Slovenian Medical Society - Section of Radiology
Languages: English
Types: Article
Subjects:
Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system,what makes them poorly immunogenic or even tolerogenic. Novel irrtmunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor-specific T-lymphocyte transfer and tumor specific monoclonal antibodies). Tumorska cepiva imajo številne prednosti v primerjavi z drugimi oblikami zdravljenja raka. Predstavljajo visokospecifično protitumorsko terapijo in jihlahko usmerimo prod antigenom, ključnim za proces maligne preobrazbe. Imajoedinstven potencial za trajni protitumorski učinek zaradi nastanka dolgoživega, za tumor specifičnega imunskega spomina. Kljub velikim pričakovanjem so dosedanji klinični poskusi cepljenja bolnikov z rakom s tumorskimi cepivi v glavnem prinesli razočaranje. Vzroki za neuspešnost tumorskih cepiv so številni. Potencialno protitumorsko populacijo limfocitov Tpredstavljajo nizkoafinitetni in maloštevilni periferni limfociti T. Večina tumorskih antigenov namreč predstavlja lastne antigene, za katere je imunski sistem toleranten. Vzporedno tumorji razvijajo različne mehanizme, s katerimi se izogibajo imunskemu sistemu in so kot taki slabo imunogeni ali celo tolerogeni. Novejše imunoterapevtske strategije so usmerjene v premagovanje imunske tolerance na tumorske antigene, povečevanje imunogenosti tumorskih cepiv in nasprotovanje mehanizmom tumorskega izogibanja imunskemu sistemu. Pristopi so številni, a še vedno daleč stran od idealnega tumorskega cepiva, ki bi uspešno zavrnilo tumor. Težave pri aktivaciji protitumorskega imunskega odziva s tumorskimi cepivi so privedle do razvoja alternativnih imunoterapevtskih strategij, ki neposredno vključujejo efektorske mehanizme imunskega odziva (adoptivni prenos limfocitov T in monoklonska protitelesa).
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