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


language: English

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


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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