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A Journal on Nephrology and Urology

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Minerva Urologica e Nefrologica 2003 March;55(1):67-79

language: English

Induction immunotherapy with IL-2Rα monoclonal antibody in kidney transplantation

Ahsan N.

Division of Nephrology and Transplantation University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School New Brunswick, NJ, USA

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The de­vel­op­ment of new im­mu­no­sup­pres­sive ­agents is de­signed to re­duce the in­ci­dence and se­ver­ity of ear­ly ­acute ­post-trans­plant re­jec­tion. One po­ten­tial tar­get for ­more spe­cif­ic im­mu­no­sup­pres­sive ther­a­py ­with mono­clo­nal anti­bod­ies is the ­high af­fin­ity α ­chain of inter­leu­kin-2 re­cep­tors (IL-2Rα). Clinical in­ves­ti­ga­tion of mu­rine IL-2Rα mono­clo­nal anti­bod­ies (IL-2Rα mAb) in re­nal trans­plan­ta­tion has in­di­cat­ed ­that a com­plete block­ade of IL-2Rα dur­ing the crit­i­cal ­first ­post-trans­plant ­months al­lows ef­fec­tive im­mu­no­proph­y­lax­is, es­pe­cial­ly in the ear­ly ­post-trans­plant pe­ri­od. Efficacy of ­these ­agents, how­ev­er, is ham­pered by ­their ­short dis­po­si­tion ­half-­lives in hu­mans and ­their im­mu­nog­e­nic­ity in the ­form of neu­tral­iz­ing hu­man anti­mouse anti­bod­ies. These in­her­ent prob­lems can be par­tial­ly over­come by chi-mer­ic, hyp­er-chi­mer­ic (hu­man­ized) prod­ucts and mul­ti­ple ­dose reg­i­mens. Both IL-2Rα mAbs: da­cliz­u­mab (hu­man­ized) and bas­i­lix­i­mab (chi­mer­ic) cur­rent­ly ap­proved for clin­i­cal use ­have ­been ­found to re­duce the fre­quen­cy of ­acute re­jec­tions in re­nal trans­plant re­cip­ients with­out an ap­par­ent in­crease in ­short-­term tox­ic­ities. In ­most trans­plant cen­ters ­where ­these ­agents are uti­lized, ­they are be­ing rou­tine­ly ad­min­is­tered as in­duc­tion im­mu­no­proph­y­lax­is in rec­om­mend­ed mul­ti­ple ­dose reg­i­mens to re­cip­ients of sol­id or­gan trans­plants. Others ­have re­strict­ed ­their use to cer­tain ­high-­risk pa­tients ­such as ­those under­go­ing mul­ti-or­gan trans­plan­ta­tion, re­cip­ients ­with ­high pan­el-re­ac­tive anti­bod­ies, African-Americans, pa­tients at ­risk for de­vel­op­ing de­layed ­graft func­tion (DGF), and chil­dren. Recently ­some in­ves­ti­ga­tors ­have suc­cess­ful­ly ad­min­is­tered ­these anti­bod­ies co-ad­min­is­tered ­with new­er im­mu­no­sup­pres­sive ­agents in lim­it­ed ­dose pro­to­cols ­thus de­vel­op­ing ­cost ef­fec­tive and sim­pli­fied reg­i­mens. Therefore, in the ab­sence of a fa­vor­able ­long-­term ef­fi­ca­cy, it is like­ly ­that ­these ­agents ­will be ad­min­is­tered in lim­it­ed ­dose pro­to­cols ­along ­with one of the mod­ula­tors of IL-2, i.e. cal­ci­neu­rin in­hib­i­tors (CNI), to a se­lect­ed ­group of pa­tients in ­whom ad­di­tion­al im­mu­no­sup­pres­sion in the ear­ly ­post-trans­plan­ta­tion pe­ri­od is de­sir­able.

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