Author/Editor		Tedesco, Francesco; Macor, Paolo
Title		Complement regulatory proteins in tumor growth
Translated title		Beljakovine, ki uravnavajo dejavnost komplementnega sistema in rast tumorjev
Type		članek
Source		Med Razgl
Vol. and No.		Letnik 43, št. Suppl 5
Publication year		2004
Volume		str. 121-4
Language		eng
Abstract		Interest in the protective role of complement against tumor growth has been raised by the recent introduction of monoclonal antibodies to tumor antigens in the treatment of some tumors. The ability of the antibodies to activate the complement system depends on several factors, including the epitope density of the target antigen, the antibody class and the efficiency of the complement system. Several inhibitors tightly regulate the latter by acting in the fluid phase on the cell membrane. Tumor cells have developed efficient mechanisms to evade complement attack, one of which consists of the overexpression of complement regulators. These proteins have been documented in tumor tissue and on cell lines, and in several instances they have been found to be inversely correlated with the amount of complement components deposited on tumor tissue and with the susceptibility of tumor cells to complement-dependent cell cytoxicity. The availability of human phage display library has enabled our group to isolate scFvs that recognize CD59 and CD46 and neutralize the functional activity of these complement regulators. The results of in vitro studies have revealed that the complement dependent cytotoxicity of B lymphoma cell lines can be enhanced by the addition of these scFvs.
Summary		Zanimanje za zaščitno vlogo komplementnega sistema proti tumorski rasti se je povečalo, ko so začeli uporabljati za zdravljenje tumorjev monoklonska protitelesa uperjena proti nekaterim tumorskim antigenom. Zmožnost protiteles, da aktivirajo komplementni sistem je odvisna od mnogih dejavnikov. Med njimi so pomembni: gostota tarčnega antigena, vrsta ali podvrsta protiteles in trenutna učinkovitost komplementnega sistema. Slednjega uravnavajo številne inhibitorske molekule, ki so dejavne v krvi, medceličnini in na celični membrani. Tumorske celice so razvile učinkovite mehanizme, s katerimi se lahko izognejo napadu komplementa. Med njimi je tudi povečano izražanje beljakovinskih regulatorskih molekul komplementnega sistema. Nekatere od njih se izražajo neposredno v tumorskem tkivu in na celicah tumorskih celičnih linij. Zanimivo je, da je količina teh sestavin pogosto obratno sorazmerna z občutljivostjo tumorja za s komplementom posredovano citotoksičnost. V naši skupini smo uspeli izdelati beljakovinski konstrukt, ki smo ga imenovali scFv, ki prepoznava regulatorski molekuli CD59 in CD46, in nevtraliziral dejavnost teh dveh molekul. Z raziskavami smo pokazali, da lahko s tretiranjem celic B celičnega limfoma in vitro z dodatkov scFv zvečamo občutljivost teh celic za od komplementa odvisna citotoksičnost.
Descriptors		NEOPLASMS COMPLEMENT INACTIVATORS ANTIGENS, CD59 CYTOTOXICITY, IMMUNOLOGIC