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Minerva Biotecnologica 1999 December;11(4):295-301

Copyright © 1999 EDIZIONI MINERVA MEDICA

lingua: Inglese

Monoclonal antibodies as therapeutic tools in cancer

Mezzanzanica D., Canevari S.

Unit of Molecular Therapies, Department of Experimental Oncology, Istituto Nazionale per lo Studio dei Tumori, Milano, Italy


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Monoclonal anti­bod­ies ­were ­derived ­more ­than 20 ­years ago, but ­only now the avail­able ­results ­from clin­i­cal stud­ies sug­gest the prom­ise of anti­body-­based ther­a­py of can­cer. The emer­gence of ­drug-resist­ant ­tumor ­cells and the insuf­fi­cient ­tumor selec­tiv­ity of con­ven­tion­al chem­o­ther­a­py, encour­aged ­research to recon­sid­er the tar­get­ing prop­er­ties of the ­immune ­system to ­improve the selec­tiv­ity of ­anti-­tumor ther­a­py. The appli­ca­tion of molec­u­lar biol­o­gy tech­nol­o­gy ­allowed improv­ing the qual­ity of anti­body by decreas­ing the ­size and pro­duc­ing human­ized or ­even total­ly ­human ­reagents. These new gen­er­a­tions af anti­bod­ies ­show ­improved ­tumor pen­e­tra­tion and a ­reduced induc­tion of ­human ­anti-­mouse anti­body ­response ­that ­impaired repet­i­tive use of anti­bod­ies of ­first gen­er­a­tion. The human­ized ­form of and ­anti-CD20 mono­clo­nal anti­bo­dy (Rituxan) rep­re­sents the ­first anti­body ­approved by the FDA for ther­a­peu­tic use in can­cer. Forty-sev­en per­cent of the ­patients ­with low-­grade lym­pho­ma resist­ant to chem­o­ther­a­py, ­showed objec­tive ­response ­after Rituxan treat­ment. The oth­er com­mer­cial­ly avail­able anti­body ­approved in Germany for use in ­colon can­cer is the 17-1A ­used as adju­vant ther­a­py for ­patients ­with Duke’s C ­colon can­cer fol­low­ing resec­tion. In ­this ­study, ­improved sur­vi­val was ­observed in anti­body treat­ed ­patients ­with min­i­mal resid­u­al dis­ease, ­instead of ­advanced dis­ease, ­with a 30% reduc­tion in ­death and a 27% reduc­tion in recur­rence. The anti­gen char­ac­ter­is­tics, as ­well as the ­site of the dis­ease ­play a sig­nif­i­cant ­role in deter­min­ing suc­cess of anti­body treat­ment. It is the ­case of ­stage III ovar­ian can­cer ­patients treat­ed intra­per­it­o­neal­ly ­with autol­o­gous lym­pho­cytes redi­rect­ed to the ­tumor by an anti­body rec­og­niz­ing ­both the ­tumor ­cells and the lym­pho­cytes. In ­this ­case ­both ­arms of the ­immune ­system are ­used ­against can­cer. The over­all ­response ­was 27%, ­with ­long last­ing com­plete respons­es. Antibodies can be ­uses ­also as immu­no­con­ju­gates to pro­vide tar­get­ing spec­i­fic­ity to cyto­tox­ic moie­ties ­like cat­a­lyt­ic tox­ins, chem­o­ther­a­peu­tic ­agents and radio­nu­clides. Promising ­results ­were ­obtained ­with all ­these mole­cules. Full exploi­ta­tion of anti­body-­based can­cer ther­a­py ­will prob­ably ­depends on the adopt­ed strat­e­gies, in par­tic­u­lar a pro­duc­tive use of anti­body ­could be as sup­ple­ment to exist­ing ther­a­pies and ­their appli­ca­tion for ­patients ­with min­i­mal resid­u­al dis­ease ­instead of ­large ­tumor mass­es.

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