194:
antibody-dependent cell–mediated cytotoxicity (ADCC) both in vitro and in vivo against ovarian cancer.,. Recently, it has been demonstrated the efficacy of a combined approach (CIK + Cetuximab) against triple negative breast cancer (TNBC), an aggressive tumor that still requires therapeutic options. Different primitive and metastatic TNBC cancer mouse models were established in mice, and the treatment CIK cells plus cetuximab significantly restrained primitive tumor growth in mice, either in patient-derived tumor xenografts or MDA-MB-231 cell line models. Moreover, this approach almost completely abolished metastasis spreading and dramatically improved survival. The antigen-specific mAb favored tumor and metastasis tissue infiltration by CIK cells, and led to an enrichment of the CD16a+ subset. Data highlight the potentiality of this novel immunotherapy strategy where a nonspecific cytotoxic cell population can be converted into tumor-specific effectors with clinical-grade antibodies, thus providing not only a therapeutic option for TNBC but also a valid alternative to more complex approaches based on chimeric antigen receptor-engineered cells.
336:
The international registry on CIK cells (IRCC) was founded in 2011 as an independent organization, dedicated to collect data about clinical trials utilizing CIK cells and subsequent analysis to determine the latest state of clinical CIK cell research. A particular focus is thereby the evaluation of
1258:
Chan, JK; Hamilton, CA; Cheung, MK; Karimi, M; Baker, J; Gall, JM; Schulz, S; Thorne, SH; Teng, NN; Contag, CH; Lum, LG; Negrin, RS (15 March 2006). "Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study".
101:
A new subclass of NK cells have been created both in vitro and in vivo. These NK cells referred to as cytokine induced memory-like natural killer cells are induced using cytokines, most commonly a mix of IL-12, IL-15, and IL-18. These NK cells are activated by these cytokines to stimulate an
193:
settings. Furthermore, it has been shown that CIK cells have a relevant expression of FcÎłRIIIa (CD16a), which can be exploited in combination with clinical-grade mAbs to redirect their activity in an antigen-specific manner. Indeed, the engagement of CD16a on CD3+CD56+ cells led to a potent
1214:
Tettamanti, Sarah; Marin, Virna; Pizzitola, Irene; Magnani, Chiara F.; Giordano
Attianese, Greta M. P.; Cribioli, Elisabetta; Maltese, Francesca; Galimberti, Stefania; Lopez, Angel F.; Biondi, Andrea; Bonnet, Dominique; Biagi, Ettore (May 2013). "Targeting of acute myeloid leukaemia by
110:
They were given the name “cytokine-induced killer” because cultivation with certain cytokines is mandatory for the maturation into terminally differentiated CIK cells. Several sources also call them natural killer cell-like T cells due to their close relationship to
1064:
Märten, A; Ziske, C; Schöttker, B; Renoth, S; Weineck, S; Buttgereit, P; Schakowski, F; von Rücker, A; Sauerbruch, T; Schmidt-Wolf, IG (2000). "Interactions between dendritic cells and cytokine-induced killer cells lead to an activation of both populations".
517:
Schmidt-Wolf, IG; Lefterova, P; Mehta, BA; Fernandez, LP; Huhn, D; Blume, KG; Weissman, IL; Negrin, RS (December 1993). "Phenotypic characterization and identification of effector cells involved in tumor cell recognition of cytokine-induced killer cells".
225:-unrestricted anti-tumor cytotoxicity against a broad range of cancer cells. Up to now the exact mechanisms of tumor recognition and targeted cytotoxicity of CIK cells is not fully understood. Besides recognition via
833:
Li, H; Yu, JP; Cao, S; Wei, F; Zhang, P; An, XM; Huang, ZT; Ren, XB (May 2007). "CD4 +CD25 + regulatory T cells decreased the antitumor activity of cytokine-induced killer (CIK) cells of lung cancer patients".
102:
infection and induce an adaptive immune response. If cocultured with target cells such as tumor targets, these NK cells have memory-like abilities and are more adapt and effective at mounting a defense.
82:
and MHC, allowing for a fast and unbiased immune reaction. This is of particular importance as harmful cells that are missing MHC markers cannot be tracked and attacked by other immune cells, such as
880:
Schmeel, LC; Schmeel, FC; Coch, C; Schmidt-Wolf, IG (8 November 2014). "Cytokine-induced killer (CIK) cells in cancer immunotherapy: report of the international registry on CIK cells (IRCC)".
1017:"Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma"
1015:
Schmidt-Wolf, IG; Finke, S; Trojaneck, B; Denkena, A; Lefterova, P; Schwella, N; Heuft, HG; Prange, G; Korte, M; Takeya, M; Dorbic, T; Neubauer, A; Wittig, B; Huhn, D (November 1999).
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in a time-sensitive schedule. These cytokines strongly stimulate the proliferation and maturation into CIK cells. After completed maturation CIK cells are transfused to the donor in
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Hontscha, C; Borck, Y; Zhou, H; Messmer, D; Schmidt-Wolf, IG (February 2011). "Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC)".
406:
CIK cells were first described by Ingo G.H. Schmidt-Wolf in 1991, who also performed the first clinical trial with CIK cells in the treatment of cancer patients in 1994.
550:"A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency"
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with an antibody-defined specificity for different tumor antigens, showed an improved selectivity and activation in targeting antigen-presenting tumor cells.
969:
Jäkel, Clara E; Schmidt-Wolf, Ingo GH (July 2014). "An update on new adoptive immunotherapy strategies for solid tumors with cytokine-induced killer cells".
86:. As a special feature, terminally differentiated CD3+CD56+ CIK cells possess the capacity for both MHC-restricted and MHC-unrestricted anti-tumor
1110:"Dendritic cells reduce number and function of CD4+CD25+ cells in cytokine-induced killer cells derived from patients with pancreatic carcinoma"
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606:"Dual-functional capability of CD3+CD56+ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity"
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or rather vaccinated DCs further improves the anti-tumor efficacy of CIK cells and joint cultivation additionally reduces the number of
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Introna, M; Pievani, A; Borleri, G; Capelli, C; Algarotti, A; Micò, C; Grassi, A; Oldani, E; Golay, J; Rambaldi, A (November 2010).
308:, autologous and allogeneic CIK cells displayed a high cytotoxic potential against a broad range of varying tumor entities, whereas
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1296:"Cytokine-induced killer cells targeted by the novel bispecific antibody CD19xCD5 (HD37xT5.16) efficiently lyse B-lymphoma cells"
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within the CIK cell culture, resulting in enhanced expansion and frequency of CD3+CD56+ cells in the amplified cell population.
1167:"Arming cytokine-induced killer cells with chimeric antigen receptors: CD28 outperforms combined CD28-OX40 "super-stimulation""
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373:. Gene-transfected CIK cells were first applied in 1999 for the treatment of ten patients in metastatic state of disease.
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463:"Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity"
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269:. Recognition is specific to tumor and virus infected cells as CIK cells do not display activity against healthy cells.
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398:, cross-linking cytotoxic effector cells with malignant targets, was enhanced compared with CIK cells alone.
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245:. These receptors and surface markers confer the capability of acting against cells that do not display the
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784:"Cytokines for the induction of antitumor effectors: The paradigm of Cytokine-Induced Killer (CIK) cells"
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221:-like phenotype. This unique combination of T-cell and NK-cell capabilities exerts a potent and widely
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78:. However, CIK cells have the ability to recognize infected or even malignant cells in the absence of
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735:"Retargeting cytokine-induced killer cell activity by CD16 engagement with clinical-grade antibodies"
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Pievani, A; Borleri, G; Pende, D; Moretta, L; Rambaldi, A; Golay, J; Introna, M (22 September 2011).
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694:"Feasibility and safety of adoptive immunotherapy with CIK cells after cord blood transplantation"
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cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor".
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Tita-Nwa, F; Moldenhauer, G; Herbst, M; Kleist, C; Ho, AD; Kornacker, M (December 2007).
90:. These properties, inter alia, rendered CIK cells attractive as a potential therapy for
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Schmidt-Wolf, IG; Negrin, RS; Kiem, HP; Blume, KG; Weissman, IL (1 July 1991).
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tumors. Particularly solid and hematologic tumor cells tend to overexpress
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649:; Smyth, MJ; Van Kaer, L (March 2004). "NKT cells: what's in a name?".
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Schmidt, J; Eisold, S; Büchler, MW; Märten, A (November 2004).
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In-vitro and in-vivo activity of CIK cells in conjunction with
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cells, both primary and metastatic. CIK cells respond to these
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of tumor burden, prolonged survival durations and improved
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were only minor. In many cases, CIK cell treatment led to
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ligands, making them a sought target of CIK cell-mediated
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In-vitro studies revealed that CIK cells, redirected by
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CIK cell efficacy in clinical trials and side effects.
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The mechanism of CIK cells is distinctive from that of
115:. Others propose to classify CIK cells as subset of
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733:Rosato Antonio, Cappuzzello Elisa (30 June 2016).
1165:Hombach, AA; Rappl, G; Abken, H (December 2013).
928:Journal of Cancer Research and Clinical Oncology
882:Journal of Cancer Research and Clinical Oncology
66:presented on infected cell surfaces, triggering
782:Rosato Antonio, Sommaggio Roberta (Aug 2017).
376:Evidence is growing that the interaction with
365:. Gene-modified CIK cells showed an increased
206:or LAK cells because they can lyse cells that
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8:
284:CIK cells, along with the administration of
249:, as has been shown by the ability to cause
161:mononuclear cells are extracted from either
135:, are capable of lysing fresh, non-cultured
698:Biology of Blood and Marrow Transplantation
213:CIK cells have, as a key feature, a double
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1366:International registry on CIK cells (IRCC)
332:International registry on CIK cells (IRCC)
304:In a large number of phase I and phase II
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276:were shown to inhibit CIK cell function.
169:. Extracted cells are ex-vivo exposed to
43:mononuclear cells with interferon-gamma (
37:peripheral blood mononuclear cells (PBMC)
1358:at the US National Library of Medicine
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288:have been experimentally used to treat
189:settings or to different recipients in
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64:major histocompatibility complex (MHC)
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548:Lu, PH; Negrin, RS (15 August 1994).
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971:Expert Opinion on Biological Therapy
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467:The Journal of Experimental Medicine
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1618:Mucosal associated invariant T cell
155:Peripheral blood mononuclear cells
14:
1654:Lymphokine-activated killer cell
1373:by the National Cancer Institute
1300:Cancer Immunology, Immunotherapy
1114:Cancer Immunology, Immunotherapy
1079:10.1097/00002371-200111000-00007
426:Lymphokine-activated killer cell
247:major histocompatibility complex
349:, researchers succeeded in the
62:Typically, immune cells detect
1217:British Journal of Haematology
836:Journal of Clinical Immunology
165:or cord blood, e.g. by simple
1:
1356:Cytokine-Induced Killer Cells
1273:10.1158/1078-0432.ccr-05-2019
801:10.1016/j.cytogfr.2017.06.003
751:10.1080/2162402X.2016.1199311
17:Cytokine-induced killer cells
1699:Type 3 innate lymphoid cells
1687:Type 2 innate lymphoid cells
1682:Type 1 innate lymphoid cells
1669:Uterine natural killer cells
1649:Cytokine-induced killer cell
983:10.1517/14712598.2014.900537
645:Godfrey, DI; MacDonald, HR;
623:10.1182/blood-2011-02-336321
292:in mice and humans with low
567:10.4049/jimmunol.153.4.1687
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788:Cytokine Growth Factor Rev
711:10.1016/j.bbmt.2010.05.015
651:Nature Reviews. Immunology
389:chimeric antigen receptors
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1312:10.1007/s00262-007-0333-0
1126:10.1007/s00262-004-0554-4
1021:British Journal of Cancer
940:10.1007/s00432-010-0887-7
894:10.1007/s00432-014-1864-3
848:10.1007/s10875-007-9076-0
1360:Medical Subject Headings
1261:Clinical Cancer Research
1067:Journal of Immunotherapy
328:modality in the future.
33:natural killer (NK) cell
1726:Hematopoietic stem cell
1485:Lymphoplasmacytoid cell
1371:Definition of CIK cells
520:Experimental Hematology
127:It has been shown that
23:) cells are a group of
1033:10.1038/sj.bjc.6690800
353:of cells ex-vivo with
210:and LAK cells cannot.
151:or LAK cell activity.
55:and recombinant human
1632:Innate lymphoid cells
1608:Natural killer T cell
554:Journal of Immunology
479:10.1084/jem.174.1.139
421:Natural killer T cell
396:bispecific antibodies
25:immune effector cells
436:Cancer immunotherapy
378:dendritic cells (DC)
326:first-line treatment
253:in non-immunogenic,
204:natural killer cells
51:, recombinant human
1600:Innate-like T cells
1480:Transitional B cell
1183:10.1038/mt.2013.192
416:Natural killer cell
314:complete remissions
369:rate and enhanced
57:interleukin (IL)-2
53:interleukin (IL)-1
27:featuring a mixed
1767:Cancer treatments
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1229:10.1111/bjh.12282
1171:Molecular Therapy
272:Immunomodulatory
175:anti-CD3 antibody
70:release, causing
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1084:
1080:
1076:
1073:(6): 502–10.
1072:
1068:
1060:
1057:
1052:
1048:
1043:
1038:
1034:
1030:
1026:
1022:
1018:
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984:
980:
976:
972:
965:
962:
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949:
945:
941:
937:
934:(2): 305–10.
933:
929:
922:
920:
916:
911:
907:
903:
899:
895:
891:
888:(5): 839–49.
887:
883:
876:
874:
870:
865:
861:
857:
853:
849:
845:
842:(3): 317–26.
841:
837:
829:
826:
821:
817:
812:
811:11577/3243034
807:
802:
797:
793:
789:
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766:
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688:
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664:
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656:
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648:
647:Kronenberg, M
641:
638:
633:
629:
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619:
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473:(1): 139–49.
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367:proliferation
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341:Future trends
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183:interleukin-2
180:
179:interleukin-1
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133:interleukin 2
130:
122:
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118:
114:
105:
103:
99:
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85:
84:T-lymphocytes
81:
77:
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50:
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30:
26:
22:
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1070:
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1059:
1024:
1020:
974:
970:
964:
931:
927:
885:
881:
839:
835:
828:
791:
787:
777:
742:
738:
728:
701:
697:
687:
657:(3): 231–7.
654:
650:
640:
613:
609:
557:
553:
523:
519:
470:
466:
405:
393:
386:
375:
351:transfection
344:
335:
310:side effects
303:
283:
271:
212:
201:
153:
126:
109:
106:Nomenclature
100:
88:cytotoxicity
61:
20:
16:
15:
1762:Lymphocytes
1731:Lymphoblast
1429:Plasmablast
1408:Lymphocytes
431:Interleukin
141:lymphokines
129:lymphocytes
1751:Categories
1545:Regulatory
1518:Helper CD4
1444:Follicular
794:: 99–105.
442:References
255:allogeneic
191:allogeneic
187:autologous
167:blood draw
159:cord blood
80:antibodies
41:cord blood
1704:LTi cells
1659:Null cell
1507:Thymocyte
267:cytolysis
259:syngeneic
123:Mechanism
76:apoptosis
1692:Nuocytes
1641:NK cells
1473:B10 cell
1330:17487487
1321:11029829
1281:16551871
1245:20084806
1237:23432359
1201:23985696
1152:24874819
1144:15185013
1135:11032841
1095:41096583
1087:11759073
1051:10576658
999:21285433
991:24673175
956:12018626
948:20407789
910:11940173
902:25381063
864:21924179
856:17468835
820:28629761
769:27622068
720:20685246
679:19442375
671:15039760
632:21821703
584:23803853
410:See also
371:toxicity
355:cytokine
294:toxicity
208:NK cells
198:Function
113:NK cells
68:cytokine
1495:T cells
1424:B1 cell
1416:B cells
1338:2599140
1192:3863798
1042:2362953
760:5007963
576:7519209
532:7694868
497:1711560
488:2118875
402:History
361:, e.g.
347:studies
306:studies
219:NK cell
149:NK cell
119:cells.
1439:Memory
1434:Plasma
1362:(MeSH)
1336:
1328:
1318:
1279:
1243:
1235:
1199:
1189:
1150:
1142:
1132:
1093:
1085:
1049:
1039:
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989:
954:
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669:
630:
582:
574:
530:
495:
485:
290:cancer
239:DNAM-1
215:T-cell
137:cancer
92:cancer
31:- and
1551:NaĂŻve
1459:Pre-B
1454:NaĂŻve
1334:S2CID
1241:S2CID
1148:S2CID
1091:S2CID
995:S2CID
952:S2CID
906:S2CID
860:S2CID
675:S2CID
610:Blood
580:S2CID
382:Tregs
359:genes
274:Tregs
263:NKG2D
251:lysis
243:NKp30
235:NKG2D
72:lysis
45:IFN-Îł
1511:αβ (
1468:cell
1326:PMID
1277:PMID
1233:PMID
1197:PMID
1140:PMID
1083:PMID
1047:PMID
987:PMID
944:PMID
898:PMID
852:PMID
816:PMID
765:PMID
716:PMID
667:PMID
628:PMID
572:PMID
528:PMID
493:PMID
363:IL-2
286:IL-2
257:and
241:and
217:and
181:and
145:IL-2
94:and
1466:reg
1316:PMC
1308:doi
1269:doi
1225:doi
1221:161
1187:PMC
1179:doi
1130:PMC
1122:doi
1075:doi
1037:PMC
1029:doi
979:doi
936:doi
932:137
890:doi
886:141
844:doi
806:hdl
796:doi
755:PMC
747:doi
706:doi
659:doi
618:doi
614:118
562:doi
558:153
483:PMC
475:doi
471:174
345:In
231:CD3
227:TCR
223:MHC
157:or
117:NKT
74:or
47:),
39:or
21:CIK
1753::
1613:γδ
1587:VM
1579:RM
1571:EM
1563:CM
1543:/
1541:17
1535:/
1527:/
1524:FH
1520:/
1332:.
1324:.
1314:.
1304:56
1302:.
1298:.
1275:.
1265:12
1263:.
1239:.
1231:.
1219:.
1195:.
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1138:.
1128:.
1118:53
1116:.
1112:.
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1081:.
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1069:.
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1025:81
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858:.
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840:27
838:.
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737:.
714:.
702:16
700:.
696:.
673:.
665:.
653:.
626:.
612:.
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592:^
578:.
570:.
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540:^
524:21
522:.
505:^
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449:^
296:.
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177:,
173:,
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1577:T
1569:T
1561:T
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1539:h
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1533:3
1531:h
1529:T
1522:T
1464:B
1400:e
1393:t
1386:v
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1283:.
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661::
655:4
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564::
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29:T
19:(
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