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Home > Journals > Minerva Urologica e Nefrologica > Past Issues > Minerva Urologica e Nefrologica 2003 March;55(1) > Minerva Urologica e Nefrologica 2003 March;55(1):67-79



A Journal on Nephrology and Urology

Indexed/Abstracted in: EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 0,536

Frequency: Bi-Monthly

ISSN 0393-2249

Online ISSN 1827-1758


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


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

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.

language: English

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