Differential internalization of hu14.18‐IL2 immunocytokine by NK and tumor cell: impact on conjugation, cytotoxicity, and targeting

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: immune synapse;    GD2 ;    IL‐;    2R;    NK cells;    melanoma;    neuroblastoma;   

DOI  :  10.1189/jlb.0710422

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Thehu14.18‐IL2(EMD273063)IC,consistingofaGD2‐specificmAbgeneticallyengineeredtotwomoleculesofIL‐2,isinclinicaltrialsfortreatmentofGD2‐expressingtumors.Anti‐tumoractivityofICinvivoandinvitroinvolvesNKcells.WestudiedthekineticsofretentionofIConthesurfaceofhumanCD25+CD16–NKcelllines(NKLandRL12)andGD2+M21melanomaafterICbindingtothecellsviaIL‐2RandGD2,respectively.ForNKcells,∼50%ofICwasinternalizedby3hand∼90%by24hofcellculture.ThedecreaseofsurfaceIClevelsonNKcellscorrelatedwiththelossoftheirabilitytobindtotumorcellsandmediateantibody‐dependentcellularcytotoxicityinvitro.UnlikeNKcells,M21cellsretained∼70%ofIConthesurfacefollowing24hofcultureandmaintainedtheabilitytobecomeconjugatedandlysedbyNKcells.WhenNKLcellswereinjectedintoM21‐bearingSCIDmice,ITdeliveryofICaugmentedNKcellmigrationintothetumor.ThesestudiesdemonstratethatonceICbindstothetumor,itispresentonthetumorsurfaceforaprolongedtime,inducingtherecruitmentofNKcellstothetumorsite,followedbytumorcellkilling...

【 授权许可】

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