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Rivista di Biologia Molecolare e Biotecnologie

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Minerva Biotecnologica 1999 December;11(4):255-60

lingua: Inglese

Tumor anti­gens rec­og­nized by anti­bod­ies

Pupa S.

Molecular Targeting Unit 12, Istituto Nazionale Tumori, Milan, Italy


The anal­y­sis of ser­o­log­i­cal respons­es to ­tumors has a ­long tra­di­tion. In the 1970s a con­sid­er­able ­amount of ­work was car­ried out by Lloyd Old’s ­group, who estab­lished the strat­e­gy of autol­o­gous typ­ing 1 by 1) the use of autol­o­gous ser­um and ­tumor-­cell ­lines ­from can­cer ­patients and 2) the use of exten­sive “absorp­tion anal­y­ses” for the def­i­ni­tion of the ­tumor spec­i­fic­ity and expres­sion pat­tern of the ­tumor immu­no­gen­ic ­cell-sur­face anti­gens. However, ­these anal­y­ses ­have not ­been ­very infor­ma­tive due to the com­plex­ity and het­ero­ge­ne­ity of the ­response. Tumor serol­o­gy of the 1980s was dom­i­nat­ed by the def­i­ni­tion of ­human ­tumor anti­gens ­using ­murine mono­clo­nal anti­bod­ies. In ­this ­case too, how­ev­er, the rec­og­ni­tion of ­tumor-asso­ciat­ed anti­gens by ­murine anti­body rep­er­toire did not ­lead to any con­clu­sions con­cern­ing immu­nog­e­nic­ity of ­such struc­tures in can­cer ­patients. In the 1990s, the avail­abil­ity of recom­bi­nant mole­cules, syn­thet­ic pep­tides and ana­lyt­ic and ­semi-quan­ti­ta­tive ­assays has ena­bled a bet­ter dis­sec­tion of humo­ral immu­nity. Antibody respons­es ­against molec­u­lar­ly ­defined intra­cel­lu­lar anti­gens (c-myb, c-myc, p53 and p21ras) and a num­ber of ­cell sur­face anti­gens, includ­ing oncop­ro­teins (HERs recep­tors), ­mucins (PEM/MUC1) and car­bo­hy­drate anti­gens (T, Tn, sia­lyl Tn) ­have ­been ­found in can­cer ­patients. Very recent­ly, by imple­ment­ing molec­u­lar clon­ing tech­niques ­into the orig­i­nal strat­e­gies of autol­o­gous typ­ing, the “SER­EX” tech­nique was devel­oped, ­that ­stands for the ser­o­log­i­cal anal­y­sis of autol­o­gous ­tumor anti­gens by recom­bi­nant cDNA expres­sion clon­ing. This new pow­er­ful tech­nique ­allowed the iden­tifi­ca­tion of ­many anti­gens rec­og­nized by anti­bod­ies ­that are now ­being eval­u­at­ed as poten­tial anti­tu­mor vac­cines.

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