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

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dc.contributor.author Reisfeld, RA
dc.contributor.author Gillies, SD
dc.contributor.author Rakhmilevich, AL
dc.contributor.author Yamane, B
dc.contributor.author Hank, JA
dc.contributor.author Gubbels, JA
dc.contributor.author Patankar, MS
dc.contributor.author Buhtoiarov, TN
dc.contributor.author Gan, J
dc.contributor.author Buhtoiarov, IN
dc.contributor.author Neal, ZC
dc.contributor.author Sondel, PM
dc.date.accessioned 2011-09-02T20:48:57Z
dc.date.available 2011-09-02T20:48:57Z
dc.date.issued 2011-04
dc.identifier.citation Buhtoiarov IN, Neal ZC, Gan J, Buhtoiarova TN, Patankar MS, Gubbels JA, Hank JA, Yamane B, Rakhmilevich AL, Reisfeld RA, Gillies SD, Sondel PM. Differential internalization of hu14.18-IL2 immunocytokine by NK and tumor cell: impact on conjugation, cytotoxicity, and targeting. J Leukoc Biol. 2011 Apr;89(4):625-38. Epub 2011 Jan 19. PubMed PMID: 21248148; PubMed Central PMCID: PMC3058817. en
dc.identifier.uri http://digital.library.wisc.edu/1793/54211
dc.description PMID: 21248148 en
dc.description.abstract The hu14.18-IL2 (EMD 273063) IC, consisting of a GD(2)-specific mAb genetically engineered to two molecules of IL-2, is in clinical trials for treatment of GD(2)-expressing tumors. Anti-tumor activity of IC in vivo and in vitro involves NK cells. We studied the kinetics of retention of IC on the surface of human CD25(+)CD16(-) NK cell lines (NKL and RL12) and GD(2)(+) M21 melanoma after IC binding to the cells via IL-2R and GD(2), respectively. For NK cells, ? 50% of IC was internalized by 3 h and ? 90% by 24 h of cell culture. The decrease of surface IC levels on NK cells correlated with the loss of their ability to bind to tumor cells and mediate antibody-dependent cellular cytotoxicity in vitro. Unlike NK cells, M21 cells retained ? 70% of IC on the surface following 24 h of culture and maintained the ability to become conjugated and lysed by NK cells. When NKL cells were injected into M21-bearing SCID mice, IT delivery of IC augmented NK cell migration into the tumor. These studies demonstrate that once IC binds to the tumor, it is present on the tumor surface for a prolonged time, inducing the recruitment of NK cells to the tumor site, followed by tumor cell killing. en
dc.description.provenance Submitted by Julie Schneider (jschneider@library.wisc.edu) on 2011-09-02T20:48:57Z No. of bitstreams: 1 Sondel_J_Leukocyte_Biology_2010.pdf: 4456187 bytes, checksum: 96ee86818f1a1bbda257f79f8e7813c7 (MD5) en
dc.description.provenance Made available in DSpace on 2011-09-02T20:48:57Z (GMT). No. of bitstreams: 1 Sondel_J_Leukocyte_Biology_2010.pdf: 4456187 bytes, checksum: 96ee86818f1a1bbda257f79f8e7813c7 (MD5) Previous issue date: 2011-04 en
dc.title Differential internalization of hu14.18-IL2 immunocytokine by NK and tumor cell: impact on conjugation, cytotoxicity, and targeting en
dc.type Article en

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