Author/Editor		Konatschnig, Thomas; Geis, Nicolas; Schultz, Stefan; Kirschfink, Michael
Title		Complement resistance impairs anti-tumour therapy
Translated title		Odpornost na komplement ovira onkološko zdravljenje
Type		članek
Source		Radiol Oncol
Vol. and No.		Letnik 40, št. 2
Publication year		2006
Volume		str. 95-105
Language		slo
Abstract		Background. Various studies during the last two decades clearly indicate that resistance of human tumour cells to autologous complement is mainly based on the expression of membrane-bound complement regulatory proteins (mCRP) like CD59, CD55 and CD46 with good evidence for a predominant role of CD59. Beyond these in vitro findings the importance of this phenomenon for the patients outcome now becomes evident from first clinical studies. Overcoming complement resistance of tumour cells is therefore considered a promising way to improve therapeutic options and prognosis in a variety of cancer diseases. In this short review two feasible approaches are discussed in more detail: (1) neutralisation of mCRP by monoclonal or recombinant antibodies and (2) gene silencing strategies to down-regulate mCRP by blocking the expression of these proteins on the RNA level using siRNA. Conclusions. As mCRP are also present on all normal tissues like endothelial cells, parenchymatous organs (liver, kidney etc.) or blood cells, mCRP blocking strategies have to be targeted selectively to malignant cells sparing the surrounding healthy tissues from the deleterious complement attack. Despite first encouraging results, translation of mCRP inhibition to improve antibody-based immunotherapy into the clinic is still a great challenge.
Summary		Izhodišča. Različne in vitro raziskave, ki so bile narejene v zadnjih dveh desetletjih, jasno kažejo, da je odpornost človeških tumorskih celic na avtologni komplement pogojena z na membrano vezanimi regulatornimi proteini komplementa (mCRP). Takšna proteina sta CD55 in CD46, najpomembnejšo vlogo pa ima CD59. Ta imunska dogajanja zelo vplivajo na potek bolezni, kar potrjujejo novejše klinične raziskave. Odpraviti odpornost na komplement obeta izboljšanje zdravljenja bolnikov z različnim rakom, s tem pa tudi izboljšanje napovedi izhoda bolezni. V pričujočem kratkem preglednem članku podrobneje predstavljamo: (1) nevtralizacijo proteinov mCRP z monoklonskimi ali rekombinantnimi protitelesi in (2) strategijo "utišanja" genov za proteine mCRP z delovanjem na nivoju RNA ob uporabi siRNA. Zaključki. Ker so proteini mCRP prisotni v vseh normalnih tkivih endotelnih celic parenhimskih organov (jetra, ledvica, itd...) in v krvnih celicah je zelo pomembno, da je blokiranje delovanja proteinov mCRP selektivno in da tako ne prizadene zdravega tkiva. Čeprav so prvi rezultati ohrabrujoči, je vplivanje na delovanje proteinov MCRP, da bi izboljšali imunoterapijo, še vedno izziv v klinični praksi.
Descriptors		NEOPLASMS COMPLEMENT INACTIVATORS IMMUNOTHERAPY ANTIBODIES, MONOCLONAL ANTIGENS, CD59