(En) Use of Blocking-Reagents for Reducing Unspecific T Cell-Activation Title

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(En) Use of Blocking-Reagents for Reducing Unspecific T Cell-Activation Title Title (en) Use of blocking-reagents for reducing unspecific T cell-activation Title (de) Verwendung von blockierenden Reagenzien zur Verringerung von unspezifischer T-Zellenaktivierung Title (fr) Utilisation de réactifs bloquants pour réduire l'activation de lymphocytes T non spécifiques Publication EP 3029067 A1 20160608 (EN) Application EP 14195645 A 20141201 Priority EP 14195645 A 20141201 Abstract (en) The present invention relates to a blocking-reagent for use in reducing unspecific T cell activation in T cell engaging therapies. The present invention further relates to pharmaceutical kit of parts and an in vitro method for evaluating unspecific T cell activation. IPC 8 full level C07K 16/24 (2006.01); A61K 39/395 (2006.01) CPC (source: EP US) A61K 35/17 (2013.01 - US); C07K 16/24 (2013.01 - EP); C07K 16/241 (2013.01 - US); C07K 16/2803 (2013.01 - US); C07K 16/2806 (2013.01 - US); C07K 16/2809 (2013.01 - US); C07K 16/2821 (2013.01 - US); C07K 16/2827 (2013.01 - US); C07K 16/2845 (2013.01 - US); C07K 16/2863 (2013.01 - US); C07K 16/2866 (2013.01 - US); C07K 16/2896 (2013.01 - US); C07K 16/3069 (2013.01 - US); G01N 33/56972 (2013.01 - US); A61K 2035/124 (2013.01 - US); C07K 2317/24 (2013.01 - US); C07K 2317/31 (2013.01 - US); C07K 2317/76 (2013.01 - EP US); C07K 2319/02 (2013.01 - US); G01N 2500/02 (2013.01 - US); G01N 2500/10 (2013.01 - US) Citation (applicant) • WO 2013092001 A1 20130627 - SYNIMMUNE GMBH [DE] • WO 9222653 A1 19921223 - GENENTECH INC [US] • US 5888508 A 19990330 - HILDRETH JAMES E [US] • US 5854070 A 19981229 - ROSE LYNN M [US] • EP 0057851 A2 19820818 - LEHMANN W MINOL HAUSTECH [DE] • WO 0170260 A1 20010927 - MILLENNIUM PHARM INC [US] • EP 2155783 B1 20130731 - AMGEN RES MUNICH GMBH [DE] • EP 2155788 B1 20120627 - MICROMET AG [DE] • WO 9954440 A1 19991028 - DOERKEN BERND [DE], et al • WO 2004106381 A1 20041209 - MICROMET AG [DE], et al • WO 2013092001 A1 20130627 - SYNIMMUNE GMBH [DE] • STAERZ UD; KANAGAWA 0; BEVAN MJ: "Hybrid antibodies can target sites for attack by T cells", NATURE, vol. 314, 1985, pages 628 - 631, XP008088110, DOI: doi:10.1038/314628a0 • PEREZ P; HOFFMAN RW; SHAW S; BLUESTONE JA; SEGAL DM: "Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody", NATURE, vol. 316, 1985, pages 354 - 356, XP001207655, DOI: doi:10.1038/316354a0 • JUNG G; HONSIK CJ; REISFELD RA; MÜLLER-EBERHARD HJ: "Activation of human peripheral blood mononuclear cells by anti-T3: Killing of tumor target cells coated with anti-target X anti-T3-conjugates", PROC NATL ACAD SCI USA, vol. 83, 1986, pages 4479 - 4483 • JUNG G; MÜLLER-EBERHARD HJ: "An in vitro model for tumor immunotherapy with antibody-heteroconjugates", IMMUNOL TODAY, vol. 9, 1988, pages 257 - 260, XP023938678, DOI: doi:10.1016/0167-5699(88)91304-7 • JUNG G; FREIMANN U; V.MARSCHALL Z; REISFELD RA; WILMANNS W: "Target cell induced T cell activation with bi- and trispecific antibody molecules", EUR J IMMUNOL, vol. 21, 1991, pages 2431 - 2435, XP000647636, DOI: doi:10.1002/eji.1830211020 • BARGOU R; LEO E; ZUGMAIER G ET AL.: "Tumor regression in cancer patients by very low doses of a T cell-engaging antibody", SCIENCE, vol. 321, 2008, pages 974 - 977 • ADAMS GP; WEINER LM: "Monoclonal antibody therapy of cancer", NAT BIOTECHNOL., vol. 23, 2005, pages 1147 - 57, XP002456710, DOI: doi:10.1038/nbt1137 • TOPP MS; KUFER P; GOKBUGET N ET AL.: "Targeted therapy with the T cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival", J CLIN ONCOL, vol. 29, 2011, pages 2493 - 2498, XP055112754, DOI: doi:10.1200/JCO.2010.32.7270 • KROESEN BJ; BUTER J; SLEIJFER DT ET AL.: "Phase I study of intravenously applied bispecific antibody in renal cell cancer patients receiving subcutaneous interleukin 2", BR J CANCER, vol. 70, 1994, pages 652 - 661 • TIBBEN JG; BOERMAN OC; MASSUGER LF ET AL.: "Pharmacokinetics, biodistribution and biological effects of intravenously administered bispecific monoclonal antibody OC/TR F(ab') in ovarian carcinoma patients", INT J CANCER, vol. 66, 1996, pages 477 - 483, XP001085380, DOI: doi:10.1002/(SICI)1097-0215(19960516)66:4<477::AID-IJC11>3.0.CO;2-5 • MAUS MV; GRUPP SA; PORTER DL; JUNE CH: "Antibody-modified T cells: CARs take the front seat for hematologic malignancies", BLOOD, vol. 123, 2014, pages 2625 - 35, XP055185132, DOI: doi:10.1182/blood-2013-11-492231 • MORGAN RA1; YANG JC; KITANO M; DUDLEY ME; LAURENCOT CM; ROSENBERG SA: "Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2", MOL THER, vol. 18, no. 4, 2010, pages 843 - 851, XP055023624, DOI: doi:10.1038/mt.2010.24 • ROELAND LAMERISA; RENEE C.G. DE BRUINA; FAMKE L. SCHNEIDERSA; PAUL M.P.; VAN BERGEN EN HENEGOUWENB; HENK M.W. VERHEULA; TANJA D. D: "Bispecific antibody platforms for cancer immunotherapy", CRIT REV ONCOL HEMATOL., vol. S1040-84, no. 14, 20 August 2014 (2014-08-20), pages 00135 - 8 • KLINGER M; BRANDL C; ZUGMAIER G; HIJAZI Y; BARGOU RC; TOPP MS; GOKBUGET N; NEUMANN S; GOEBELER M; VIARDOT A: "Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3- bispecific BiTE antibody blinatumomab", BLOOD, vol. 119, 2012, pages 6226 - 33 • BRENTJENS RJ; DAVILA ML; RIVIERE , PARK J; WANG X; COWELL LG; BARTIDO S; STEFANSKI J; TAYLOR C; OLSZEWSKA M; BORQUEZ- OJEDA 0: "CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia", SCI TRANSL MED, vol. 5, 2013, pages 1 - 9 • LEE DW; GARDNER R; PORTER DL; LOUIS CU; AHMED N; JENSEN M; GRUPP SA; MACKALL CL: "Current concepts in the diagnosis and management of cytokine release syndrome", BLOOD, vol. 124, no. 2, 10 July 2014 (2014-07-10), pages 188 - 95, XP055313556, DOI: doi:10.1182/ blood-2014-05-552729 • MOLEMA G; TERVAERT JW; KROESEN BJ; HELFRICH W; MEIJER DK; DE LEIJ LF: "CD3 directed bispecific antibodies induce increased lymphocyte-endothelial cell interactions in vitro", BR J CANCER, vol. 82, 2000, pages 472 - 479, XP000944237, DOI: doi:10.1054/bjoc.1999.0945 • HOLT LJ1; HERRING C; JESPERS LS; WOOLVEN BP; TOMLINSON IM: "Domain antibodies: proteins for therapy", TRENDS BIOTECHNOL., vol. 21, no. 11, November 2003 (2003-11-01), pages 484 - 90, XP004467495, DOI: doi:10.1016/j.tibtech.2003.08.007 • III CR1; GONZALES JN; HOUTZ EK; LUDWIG JR; MELCHER ED; HALE JE; POURMAND R; KEIVENS VM; MYERS L; BEIDLER K: "Design and construction of a hybrid immunoglobulin domain with properties of both heavy and light chain variable regions", PROTEIN ENG, vol. 10, no. 8, August 1997 (1997-08-01), pages 949 - 57 • MARTIN F1; TONIATTI C; SALVATI AL; VENTURINI S; CILIBERTO G; CORTESE R; SOLLAZZO M: "The affinity-selection of a minibody polypeptide inhibitor of human interleukin-6", EMBO J., vol. 13, no. 22, 15 November 1994 (1994-11-15), pages 5303 - 9, XP002076260 • TRAUNECKER A; LANZAVECCHIA A; KARJALAINEN K: "Bispecific single chain molecules (Janusins) target cytotoxic lymphocytes on HIV infected cells", EMBO J., vol. 10, no. 12, December 1991 (1991-12-01), pages 3655 - 9, XP000232579 • TRAUNECKER A; LANZAVECCHIA A; KARJALAINEN K.: "Janusin: new molecular design for bispecific reagents", INT J CANCER SUPPL., vol. 7, 1992, pages 51 - 2, XP009171574 • SILVERMAN J1; LIU Q; BAKKER A; TO W; DUGUAY A; ALBA BM; SMITH R; RIVAS A; LI P; LE H: "Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains", NAT BIOTECHNOL., vol. 23, no. 12, 20 November 2005 (2005-11-20), pages 1556 - 61, XP009088629, DOI: doi:10.1038/nbt1166 • TAN SM: "The leucocyte fl2 (CD18) integrins: the structure, functional regulation and signalling properties", BIOSCI REP., vol. 32, no. 3, June 2012 (2012-06-01), pages 241 - 69 • EDWARD F. PLOW; THOMAS A. HAAS; LI ZHANG; JOSEPH LOFTUS; JEFFREY W. SMITH: "Ligand Binding to Integrins", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 275, 21 July 2000 (2000-07-21), pages 21785 - 21788 • SANCHEZ-MADRID F.; NAGY J.A.; ROBBINS E.; SIMON P.; SPRINGER T.: "The lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule", J. EXP. MED., vol. 158, 1983, pages 1785 - 1803, XP000606523, DOI: doi:10.1084/jem.158.6.1785 • BEATTY ET AL.: "J. Definition of a common leukocyte cell-surface antigen (Lp95-150) associated with diverse cell-mediated immune functions", J. IMMUNOL., vol. 131, 1983, pages 2913 - 2918 • ULBRICH H; ERIKSSON EE; LINDBOM L: "Leukocyte and endothelial cell adhesion molecules as targets for therapeutic interventions in inflammatory disease", TRENDS PHARMACOL SCI, vol. 24, 2003, pages 640 - 647, XP004476617, DOI: doi:10.1016/j.tips.2003.10.004 • RUSNAK JM; KOPECKY SL; CLEMENTS IP; GIBBONS RJ; HOLLAND AE; PETERMAN HS; MARTIN JS; SAOUD JB; FELDMAN RL; BREISBLATT WM: "An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study", AM J CARDIOL, vol. 88, 2001, pages 482 - 487 • BOWEN JD; PETERSDORF SH; RICHARDS TL; MARAVILLA KR; DALE DC; PRICE TH; ST JOHN TP; YU AS: "Phase I study of a humanized anti- CD11/CD18 monoclonal antibody in multiple sclerosis", CLIN PHARMACOL THER, vol. 64, 1998, pages 339 - 346 • RHEE P; MORRIS J; DURHAM R; HAUSER C; CIPOLLE M; WILSON R; LUCHETTE F; MCSWAIN N; MILLER R: "Recombinant humanized monoclonal antibody against CD18 (rhuMAb CD18) in traumatic hemorrhagic shock: results of a phase II clinical trial. Traumatic Shock Group", J TRAUMA, vol. 49, 2000, pages 611 - 619 • BARAN KW; NGUYEN M; MCKENDALL GR; LAMBREW CT; DYKSTRA G; PALMERI ST; GIBBONS RJ; BORZAK S; SOBEL BE; GOURLAY SG: "Limitation of Myocardial Infarction Following Thrombolysis in Acute Myocardial Infarction (LIMIT AMI) Study Group.
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