Title:
SPNS2 NEUTRALIZING ANTIBODY
Document Type and Number:
WIPO Patent Application WO/2019/194314
Kind Code:
A1
Abstract:
The purpose of the present invention is to provide an antibody that can be expected to have a therapeutic effect in autoimmune diseases and anticancer treatment by inhibiting S1P transport by SPNS2 to thereby inhibit lymphocyte migration. The present invention is an SPNS2 neutralizing antibody or a fragment thereof, or a derivative thereof, that specifically binds to vertebrate SPNS2 and has lymphocyte migration inhibitory activity through S1P transport inhibition.
More Like This:
Inventors:
HIBIYA KENTA (JP)
KANAMARU YUSUKE (JP)
KATO HIROTSUGU (JP)
KANAMARU YUSUKE (JP)
KATO HIROTSUGU (JP)
Application Number:
PCT/JP2019/015208
Publication Date:
October 10, 2019
Filing Date:
April 05, 2019
Export Citation:
Assignee:
TEIJIN PHARMA LTD (JP)
International Classes:
C07K16/18; A61K35/12; A61K35/76; A61K39/395; A61K45/00; A61K48/00; A61P35/00; A61P35/02; A61P37/06; A61P43/00; C07K16/46; C12N1/15; C12N1/19; C12N1/21; C12N5/10; C12N15/13; C12N15/63; C12P21/08
Domestic Patent References:
| WO2014132647A1 | 2014-09-04 | |||
| WO2013180238A1 | 2013-12-05 |
Foreign References:
| JP2013059273A | 2013-04-04 | |||
| JP2010077045A | 2010-04-08 | |||
| JP5885154B2 | 2016-03-15 |
Other References:
NAKAJIMA H ET AL.: "Human myeloid cells express an activating ILT receptor (ILT1) that associates with Fc receptor gamma-chain", J. IMMUNOL., vol. 162, no. 1, 1999, pages 5 - 8, XP003014703
NAGAHASHI M ET AL.: "Sphingosine-1-phosphate transporters as targets for cancer therapy", BIOMED RES. INT., 2014, pages 1 - 7, XP055643071, DOI: 10.1155/2014/651727
SPIEGEL, S.MILSTIEN, S.: "Sphingosine-1-phosphate: an enigmatic signalling lipid", NAT REV MOL CELL BIOL, vol. 4, no. 5, 2003, pages 397 - 407, XP008077014
LIU, Y. ET AL.: "Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation", J CLIN INVEST, vol. 106, no. 8, 2000, pages 951 - 61, XP002453938, DOI: 10.1172/JCI10905
ALLENDE, ML. ET AL.: "Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration", J BIOL CHEM., vol. 279, no. 15, 9 April 2004 (2004-04-09), pages 15396 - 401
MEANS, CK. ET AL.: "S 1 P 1 receptor localization confers selectivity for Gi-mediated cAMP and contractile responses", J BIOL CHEM., vol. 283, no. 18, 2 May 2008 (2008-05-02), pages 11954 - 63
O'SULLIVAN, C.DEV, K. K.: "The structure and function of the S1P1 receptor", TRENDS PHARMACOL SCI, vol. 34, no. 7, 2013, pages 401 - 12, XP055422413, DOI: 10.1016/j.tips.2013.05.002
MACLENNAN, A. J. ET AL.: "An essentialrole for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability", EUR J NEUROSCI, vol. 14, no. 2, 2001, pages 203 - 9
MACLENNAN, A. J. ET AL.: "The S1P2 sphingosine 1-phosphate receptor is essential for auditory and vestibular function", HEAR RES, vol. 220, no. 1-2, 2006, pages 38 - 48, XP025083464, DOI: 10.1016/j.heares.2006.06.016
KONO, M. ET AL.: "The sphingosine-1-phosphatereceptors S1P1, S1P2, and S1P3 function coordinatelyduring embryonic angiogenesis", J BIOL CHEM, vol. 279, no. 28, 2004, pages 29367 - 73
NOFER, J. R. ET AL.: "HDLinduces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3", J CLIN INVEST, vol. 113, no. 4, 2004, pages 569 - 81
SANNA, M. G. ET AL.: "Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and GeneticEvidence for Direct S 1P3 Regulation of Mouse Cardiac Conduction", MOL PHARMACOL, vol. 89, no. 1, 2016, pages 176 - 86
MEANS, C. K. ET AL.: "Sphingosinel-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury", AM J PHYSIOL HEART CIRC PHYSIOL, vol. 292, no. 6, 2007, pages H2944 - 51
GOLFIER, S. ET AL.: "Shaping of terminal megakaryocyte differentiation and proplateletdevelopment by sphingosine-1-phosphatereceptor S1P4", FASEB J, vol. 24, no. 12, 2010, pages 4701 - 10
WANG, W. ET AL.: "Type 4 sphingosine 1-phosphate G protein-coupled receptor (S1P4) transduces SIP effects on T cell proliferation and cytokine secretion without signalingmigration", FASEB J, vol. 19, no. 12, 2005, pages 1731 - 3
SCHULZE, T. ET AL.: "Sphingosine-1-phospate receptor 4 (S1P4) deficiency profoundly affects dendritic cell function and TH17-cell differentiation in a murine model", FASEB J, vol. 25, no. 11, 2011, pages 4024 - 36, XP055165241, DOI: 10.1096/fj.10-179028
JAILLARD, C. ET AL.: "Edg8/S lP5: an oligodendroglial receptor with dual function on process retraction and cell survival", J NEUROSCI, vol. 25, no. 6, 2005, pages 1459 - 69, XP002512297, DOI: 10.1523/JNEUROSCI.4645-04.2005
JENNE, C. N. ET AL.: "T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow", J EXP MED., vol. 206, no. 11, 2009, pages 2469 - 81
LO, C. G. ET AL.: "Cyclical modulation of sphingosine-1-phosphatereceptor 1 surface expression during lymphocyte recirculationand relationship to lymphoidorgan transit", J EXP MED., vol. 201, no. 2, 2005, pages 291 - 301
CHIBA K: "A new therapeutic approach for autoimmune diseases by the sphingosine 1-phosphate receptor modulator, fingolimod (FTY720", NIHON RINSHO MENEKI GAKKAI KAISHI, vol. 32, no. 2, April 2009 (2009-04-01), pages 92 - 101
MATLOUBIAN, M. ET AL.: "Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on SIP receptor 1", NATURE, vol. 427, no. 6972, 2004, pages 355 - 60, XP002357815, DOI: 10.1038/nature02284
SCHWAB, S. R.CYSTER, J. G.: "Finding a way out: lymphocyte egress from lymphoid organs", NAT IMMUNOL, vol. 8, no. 12, 2007, pages 1295 - 301
NAGAHASHI, M. ET AL.: "Sphingosine-1-phosphatetransporters as targetsfor cancer therapy", BIOMED RES INT, vol. 2014, 2014, pages 651727
OSBORNE, N. ET AL.: "The spinster homolog, two of hearts, is required for sphingosine 1-phosphate signaling in zebrafish", CURR BIOL, vol. 18, no. 23, 9 December 2008 (2008-12-09), pages 1882 - 8, XP025884213, DOI: 10.1016/j.cub.2008.10.061
KAWAHARA, A. ET AL.: "The sphingolipidtransporter spns2 functions in migration of zebrafish myocardial precursors", SCIENCE, vol. 323, no. 5913, 2009, pages 524 - 7
FUKUHARA, S. ET AL.: "The sphingosine-1-phosphatetransporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice", J CLIN INVEST, vol. 122, no. 4, 2012, pages 1416 - 26
NIJNIK, A. ET AL.: "The role of sphingosine-1-phosphate transporterSpns2 in immune systemfunction", J IMMUNOL, vol. 189, no. 1, 2012, pages 102 - 11
HISANO, Y. ET AL.: "Mouse SPNS2 functions as a sphingosine-1-phosphate transporterin vascular endothelial cells", PLOS ONE, vol. 7, no. 6, 2012, pages e38941
NAGAHASHI, M. ET AL.: "Spns2, a transporter of phosphorylatedsphingoid bases, regulates their blood and lymph levels, and the lymphatic network", FASEB J, vol. 27, no. 3, 2013, pages 1001 - 11
PERLAND, E. ET AL.: "Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression", OPEN BIOL, vol. 7, no. 9, September 2017 (2017-09-01), pages 170142
DONOVIEL, M. S. ET AL.: "Spinster 2, a sphingosine-1-phosphate transporter, plays a critical role in inflammatory and autoimmune diseases", FASEB J, vol. 29, no. 12, 2015, pages 5018 - 28
VAN DER WEYDEN, L. ET AL.: "Genome-widein vivo screen identifies novel host regulators of metastatic colonization", NATURE, vol. 541, no. 7636, 2017, pages 233 - 236
MATSUURA, M. ET AL.: "Effect of FTY720, a novel immunosuppressant, on adjuvant-inducedarthritis in rats", INFLAMM RES, vol. 49, no. 8, 2000, pages 404 - 10
WANG, F. ET AL.: "Reduction of CD4 positive T cells and improvement of pathologicalchanges of collagen-induced arthritis by FTY720", EUR J PHARMACOL, vol. 573, no. 1-3, 2007, pages 230 - 40, XP022276560, DOI: 10.1016/j.ejphar.2007.07.029
DEGUCHI, Y. ET AL.: "The SIP receptor modulator FTY720 prevents the development of experimentalcolitis in mice", ONCOL REP, vol. 16, no. 4, 2006, pages 699 - 703
IDZKO, M. ET AL.: "Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function", J CLIN INVEST, vol. 116, no. 11, 2006, pages 2935 - 44, XP002757030, DOI: 10.1172/JCI28295
ANDO, S. ET AL.: "FTY720 exerts a survival advantage through the prevention of end-stageglomerular inflammation in lupus-prone BXSB mice", BIOCHEM BIOPHYS RES COMMUN, vol. 394, no. 3, 2010, pages 804 - 10
OKAZAKI, H. ET AL.: "Effects of FTY720 in MRL-lpr/lpr mice: therapeutic potential in systemic lupus erythematosus", J RHEUMATOL, vol. 29, no. 4, 2002, pages 707 - 16
SUI, M. ET AL.: "The sphingosine-1-phosphate receptor agonist FTY720 prevents the development of anti-glomerular basement membrane glomerulonephritis", MOL BIOL REP, vol. 39, no. 1, 2012, pages 389 - 97, XP019981579, DOI: 10.1007/s11033-011-0750-1
HABICHT, A. ET AL.: "Novel insights into the mechanism of action of FTY720 in a transgenic model of allograft rejection: implications for therapy of chronic rejection", J IMMUNOL, vol. 176, no. 1, 2006, pages 36 - 42
D'AMBROSIO, D.: "Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases", THER ADV CHRONIC DIS, vol. 7, no. 1, 2016, pages 18 - 33, XP055422397, DOI: 10.1177/2040622315617354Therapeutic
BRINKMANN, V. ET AL.: "The immune modulator FTY720 targets sphingosine 1-phosphate receptors", J BIOL CHEM., vol. 277, no. 24, 2002, pages 21453 - 7, XP002264445, DOI: 10.1074/jbc.C200176200
KAPPOS, L. ET AL.: "A placebo-controlledtrial of oral fingolimod in relapsing multiple sclerosis", N ENGL J MED, vol. 362, no. 5, 2010, pages 387 - 401, XP002660555, DOI: 10.1056/nejmoa0909494
COHEN, J. A. ET AL.: "Oralfingolimod or intramuscularinterferon for relapsingmultiple sclerosis", N ENGL J MED, vol. 362, no. 5, 2010, pages 402 - 15
KOYRAKH, L. ET AL.: "The heart rate decrease caused by acute FTY720 administration is mediated by the G protein-gated potassium channel I", AM J TRANSPLANT, vol. 5, no. 3, 2005, pages 529 - 36, XP002562406, DOI: 10.1111/j.1600-6143.2005.00754.x
HOCH, M. ET AL.: "Effectof ponesimod, a selectiveSlPl receptor modulator, on the QT interval in healthy individuals", BASIC CLIN PHARMACOL TOXICOL, vol. 116, no. 5, 2015, pages 429 - 37
LEGANGNEUX, E. ET AL.: "Cardiac Effects of Siponimod (BAF312) Re-initiation After Variable Periods of Drug Discontinuation in Healthy Subjects", CLIN THER, vol. 38, no. 3, 2016, pages 631 - 45, XP029447064, DOI: 10.1016/j.clinthera.2016.01.021
JAPANESE SKIN CANCER SOCIETY: "Guidelines for Medication of Malignant Melanoma", SKIN CANCER, vol. 32, no. 1, 2016, pages 2017
SMYTH, M. J. ET AL.: "NKG2Dfunction protects the host from tumor initiation", J EXP MED., vol. 202, no. 5, 2005, pages 583 - 8
XIA, A. L. ET AL.: "Chimeric-antigenreceptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities", ONCOTARGET, vol. 8, no. 52, 2017, pages 90521 - 90531, XP055452550, DOI: 10.18632/oncotarget.19361
KIM, S. ET AL.: "In vivonatural killer cell activities revealed by natural killer cell-deficient mice", PROC NATL ACAD SCI USA, vol. 97, no. 6, 2000, pages 2731 - 6
ROBERT, C. ET AL.: "Nivolumab in previously untreated melanoma without BRAF mutation", N ENGL J MED, vol. 372, no. 4, 2015, pages 320 - 30
SCHACHTER, J. ET AL.: "Pembrolizumabversus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006", LANCET, vol. 390, no. 10105, 2017, pages 1853 - 1862, XP085238791, DOI: 10.1016/S0140-6736(17)31601-X
MOCSAI, A. ET AL.: "What is the future of targeted therapy in rheumatology: biologies or small molecules?", BMC MED, vol. 12, 2014, pages 43, XP021178782, DOI: 10.1186/1741-7015-12-43
"NCBI", Database accession no. NP 001118230
TAKETO TANAKA ET AL., KEIO J. MED., vol. 60, pages 37 - 46
KABAT ET AL., THE JOURNAL OF IMMUNOLOGY, vol. 147, no. 5, 1991, pages 1709 - 1719
AL-LAZIKANI ET AL., JOURNAL OF MOLECULAR BIOLOGY, vol. 273, no. 4, 1997, pages 927 - 948
EDELMAN ET AL., PROC. NATL. ACAD. SCI USA, vol. 63, 1969, pages 78 - 85
MILSTEIN ET AL., NATURE (ENGLAND, vol. 305, no. 5934, 6 October 1983 (1983-10-06), pages 537 - 540
MILSTEIN ET AL., NATURE, vol. 305, no. 5934, 1983, pages 537 - 540
TAKETO TANAKA ET AL., THE KEIO JOURNAL OF MEDICINE, vol. 60, pages 37 - 46
REMINGTON: "The Science and Practice of Pharmacy", 2000, LIPPINCOTT WILLIAMS & WILKINS
KOHLER ET AL., NATURE, vol. 256, 1975, pages 495 - 497
JOURNAL OF MOLECULAR BIOLOGY, vol. 48, 1970, pages 443 - 453
NAGAHASHI M ET AL.: "Sphingosine-1-phosphate transporters as targets for cancer therapy", BIOMED RES. INT., 2014, pages 1 - 7, XP055643071, DOI: 10.1155/2014/651727
SPIEGEL, S.MILSTIEN, S.: "Sphingosine-1-phosphate: an enigmatic signalling lipid", NAT REV MOL CELL BIOL, vol. 4, no. 5, 2003, pages 397 - 407, XP008077014
LIU, Y. ET AL.: "Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation", J CLIN INVEST, vol. 106, no. 8, 2000, pages 951 - 61, XP002453938, DOI: 10.1172/JCI10905
ALLENDE, ML. ET AL.: "Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration", J BIOL CHEM., vol. 279, no. 15, 9 April 2004 (2004-04-09), pages 15396 - 401
MEANS, CK. ET AL.: "S 1 P 1 receptor localization confers selectivity for Gi-mediated cAMP and contractile responses", J BIOL CHEM., vol. 283, no. 18, 2 May 2008 (2008-05-02), pages 11954 - 63
O'SULLIVAN, C.DEV, K. K.: "The structure and function of the S1P1 receptor", TRENDS PHARMACOL SCI, vol. 34, no. 7, 2013, pages 401 - 12, XP055422413, DOI: 10.1016/j.tips.2013.05.002
MACLENNAN, A. J. ET AL.: "An essentialrole for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability", EUR J NEUROSCI, vol. 14, no. 2, 2001, pages 203 - 9
MACLENNAN, A. J. ET AL.: "The S1P2 sphingosine 1-phosphate receptor is essential for auditory and vestibular function", HEAR RES, vol. 220, no. 1-2, 2006, pages 38 - 48, XP025083464, DOI: 10.1016/j.heares.2006.06.016
KONO, M. ET AL.: "The sphingosine-1-phosphatereceptors S1P1, S1P2, and S1P3 function coordinatelyduring embryonic angiogenesis", J BIOL CHEM, vol. 279, no. 28, 2004, pages 29367 - 73
NOFER, J. R. ET AL.: "HDLinduces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3", J CLIN INVEST, vol. 113, no. 4, 2004, pages 569 - 81
SANNA, M. G. ET AL.: "Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and GeneticEvidence for Direct S 1P3 Regulation of Mouse Cardiac Conduction", MOL PHARMACOL, vol. 89, no. 1, 2016, pages 176 - 86
MEANS, C. K. ET AL.: "Sphingosinel-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury", AM J PHYSIOL HEART CIRC PHYSIOL, vol. 292, no. 6, 2007, pages H2944 - 51
GOLFIER, S. ET AL.: "Shaping of terminal megakaryocyte differentiation and proplateletdevelopment by sphingosine-1-phosphatereceptor S1P4", FASEB J, vol. 24, no. 12, 2010, pages 4701 - 10
WANG, W. ET AL.: "Type 4 sphingosine 1-phosphate G protein-coupled receptor (S1P4) transduces SIP effects on T cell proliferation and cytokine secretion without signalingmigration", FASEB J, vol. 19, no. 12, 2005, pages 1731 - 3
SCHULZE, T. ET AL.: "Sphingosine-1-phospate receptor 4 (S1P4) deficiency profoundly affects dendritic cell function and TH17-cell differentiation in a murine model", FASEB J, vol. 25, no. 11, 2011, pages 4024 - 36, XP055165241, DOI: 10.1096/fj.10-179028
JAILLARD, C. ET AL.: "Edg8/S lP5: an oligodendroglial receptor with dual function on process retraction and cell survival", J NEUROSCI, vol. 25, no. 6, 2005, pages 1459 - 69, XP002512297, DOI: 10.1523/JNEUROSCI.4645-04.2005
JENNE, C. N. ET AL.: "T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow", J EXP MED., vol. 206, no. 11, 2009, pages 2469 - 81
LO, C. G. ET AL.: "Cyclical modulation of sphingosine-1-phosphatereceptor 1 surface expression during lymphocyte recirculationand relationship to lymphoidorgan transit", J EXP MED., vol. 201, no. 2, 2005, pages 291 - 301
CHIBA K: "A new therapeutic approach for autoimmune diseases by the sphingosine 1-phosphate receptor modulator, fingolimod (FTY720", NIHON RINSHO MENEKI GAKKAI KAISHI, vol. 32, no. 2, April 2009 (2009-04-01), pages 92 - 101
MATLOUBIAN, M. ET AL.: "Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on SIP receptor 1", NATURE, vol. 427, no. 6972, 2004, pages 355 - 60, XP002357815, DOI: 10.1038/nature02284
SCHWAB, S. R.CYSTER, J. G.: "Finding a way out: lymphocyte egress from lymphoid organs", NAT IMMUNOL, vol. 8, no. 12, 2007, pages 1295 - 301
NAGAHASHI, M. ET AL.: "Sphingosine-1-phosphatetransporters as targetsfor cancer therapy", BIOMED RES INT, vol. 2014, 2014, pages 651727
OSBORNE, N. ET AL.: "The spinster homolog, two of hearts, is required for sphingosine 1-phosphate signaling in zebrafish", CURR BIOL, vol. 18, no. 23, 9 December 2008 (2008-12-09), pages 1882 - 8, XP025884213, DOI: 10.1016/j.cub.2008.10.061
KAWAHARA, A. ET AL.: "The sphingolipidtransporter spns2 functions in migration of zebrafish myocardial precursors", SCIENCE, vol. 323, no. 5913, 2009, pages 524 - 7
FUKUHARA, S. ET AL.: "The sphingosine-1-phosphatetransporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice", J CLIN INVEST, vol. 122, no. 4, 2012, pages 1416 - 26
NIJNIK, A. ET AL.: "The role of sphingosine-1-phosphate transporterSpns2 in immune systemfunction", J IMMUNOL, vol. 189, no. 1, 2012, pages 102 - 11
HISANO, Y. ET AL.: "Mouse SPNS2 functions as a sphingosine-1-phosphate transporterin vascular endothelial cells", PLOS ONE, vol. 7, no. 6, 2012, pages e38941
NAGAHASHI, M. ET AL.: "Spns2, a transporter of phosphorylatedsphingoid bases, regulates their blood and lymph levels, and the lymphatic network", FASEB J, vol. 27, no. 3, 2013, pages 1001 - 11
PERLAND, E. ET AL.: "Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression", OPEN BIOL, vol. 7, no. 9, September 2017 (2017-09-01), pages 170142
DONOVIEL, M. S. ET AL.: "Spinster 2, a sphingosine-1-phosphate transporter, plays a critical role in inflammatory and autoimmune diseases", FASEB J, vol. 29, no. 12, 2015, pages 5018 - 28
VAN DER WEYDEN, L. ET AL.: "Genome-widein vivo screen identifies novel host regulators of metastatic colonization", NATURE, vol. 541, no. 7636, 2017, pages 233 - 236
MATSUURA, M. ET AL.: "Effect of FTY720, a novel immunosuppressant, on adjuvant-inducedarthritis in rats", INFLAMM RES, vol. 49, no. 8, 2000, pages 404 - 10
WANG, F. ET AL.: "Reduction of CD4 positive T cells and improvement of pathologicalchanges of collagen-induced arthritis by FTY720", EUR J PHARMACOL, vol. 573, no. 1-3, 2007, pages 230 - 40, XP022276560, DOI: 10.1016/j.ejphar.2007.07.029
DEGUCHI, Y. ET AL.: "The SIP receptor modulator FTY720 prevents the development of experimentalcolitis in mice", ONCOL REP, vol. 16, no. 4, 2006, pages 699 - 703
IDZKO, M. ET AL.: "Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function", J CLIN INVEST, vol. 116, no. 11, 2006, pages 2935 - 44, XP002757030, DOI: 10.1172/JCI28295
ANDO, S. ET AL.: "FTY720 exerts a survival advantage through the prevention of end-stageglomerular inflammation in lupus-prone BXSB mice", BIOCHEM BIOPHYS RES COMMUN, vol. 394, no. 3, 2010, pages 804 - 10
OKAZAKI, H. ET AL.: "Effects of FTY720 in MRL-lpr/lpr mice: therapeutic potential in systemic lupus erythematosus", J RHEUMATOL, vol. 29, no. 4, 2002, pages 707 - 16
SUI, M. ET AL.: "The sphingosine-1-phosphate receptor agonist FTY720 prevents the development of anti-glomerular basement membrane glomerulonephritis", MOL BIOL REP, vol. 39, no. 1, 2012, pages 389 - 97, XP019981579, DOI: 10.1007/s11033-011-0750-1
HABICHT, A. ET AL.: "Novel insights into the mechanism of action of FTY720 in a transgenic model of allograft rejection: implications for therapy of chronic rejection", J IMMUNOL, vol. 176, no. 1, 2006, pages 36 - 42
D'AMBROSIO, D.: "Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases", THER ADV CHRONIC DIS, vol. 7, no. 1, 2016, pages 18 - 33, XP055422397, DOI: 10.1177/2040622315617354Therapeutic
BRINKMANN, V. ET AL.: "The immune modulator FTY720 targets sphingosine 1-phosphate receptors", J BIOL CHEM., vol. 277, no. 24, 2002, pages 21453 - 7, XP002264445, DOI: 10.1074/jbc.C200176200
KAPPOS, L. ET AL.: "A placebo-controlledtrial of oral fingolimod in relapsing multiple sclerosis", N ENGL J MED, vol. 362, no. 5, 2010, pages 387 - 401, XP002660555, DOI: 10.1056/nejmoa0909494
COHEN, J. A. ET AL.: "Oralfingolimod or intramuscularinterferon for relapsingmultiple sclerosis", N ENGL J MED, vol. 362, no. 5, 2010, pages 402 - 15
KOYRAKH, L. ET AL.: "The heart rate decrease caused by acute FTY720 administration is mediated by the G protein-gated potassium channel I", AM J TRANSPLANT, vol. 5, no. 3, 2005, pages 529 - 36, XP002562406, DOI: 10.1111/j.1600-6143.2005.00754.x
HOCH, M. ET AL.: "Effectof ponesimod, a selectiveSlPl receptor modulator, on the QT interval in healthy individuals", BASIC CLIN PHARMACOL TOXICOL, vol. 116, no. 5, 2015, pages 429 - 37
LEGANGNEUX, E. ET AL.: "Cardiac Effects of Siponimod (BAF312) Re-initiation After Variable Periods of Drug Discontinuation in Healthy Subjects", CLIN THER, vol. 38, no. 3, 2016, pages 631 - 45, XP029447064, DOI: 10.1016/j.clinthera.2016.01.021
JAPANESE SKIN CANCER SOCIETY: "Guidelines for Medication of Malignant Melanoma", SKIN CANCER, vol. 32, no. 1, 2016, pages 2017
SMYTH, M. J. ET AL.: "NKG2Dfunction protects the host from tumor initiation", J EXP MED., vol. 202, no. 5, 2005, pages 583 - 8
XIA, A. L. ET AL.: "Chimeric-antigenreceptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities", ONCOTARGET, vol. 8, no. 52, 2017, pages 90521 - 90531, XP055452550, DOI: 10.18632/oncotarget.19361
KIM, S. ET AL.: "In vivonatural killer cell activities revealed by natural killer cell-deficient mice", PROC NATL ACAD SCI USA, vol. 97, no. 6, 2000, pages 2731 - 6
ROBERT, C. ET AL.: "Nivolumab in previously untreated melanoma without BRAF mutation", N ENGL J MED, vol. 372, no. 4, 2015, pages 320 - 30
SCHACHTER, J. ET AL.: "Pembrolizumabversus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006", LANCET, vol. 390, no. 10105, 2017, pages 1853 - 1862, XP085238791, DOI: 10.1016/S0140-6736(17)31601-X
MOCSAI, A. ET AL.: "What is the future of targeted therapy in rheumatology: biologies or small molecules?", BMC MED, vol. 12, 2014, pages 43, XP021178782, DOI: 10.1186/1741-7015-12-43
"NCBI", Database accession no. NP 001118230
TAKETO TANAKA ET AL., KEIO J. MED., vol. 60, pages 37 - 46
KABAT ET AL., THE JOURNAL OF IMMUNOLOGY, vol. 147, no. 5, 1991, pages 1709 - 1719
AL-LAZIKANI ET AL., JOURNAL OF MOLECULAR BIOLOGY, vol. 273, no. 4, 1997, pages 927 - 948
EDELMAN ET AL., PROC. NATL. ACAD. SCI USA, vol. 63, 1969, pages 78 - 85
MILSTEIN ET AL., NATURE (ENGLAND, vol. 305, no. 5934, 6 October 1983 (1983-10-06), pages 537 - 540
MILSTEIN ET AL., NATURE, vol. 305, no. 5934, 1983, pages 537 - 540
TAKETO TANAKA ET AL., THE KEIO JOURNAL OF MEDICINE, vol. 60, pages 37 - 46
REMINGTON: "The Science and Practice of Pharmacy", 2000, LIPPINCOTT WILLIAMS & WILKINS
KOHLER ET AL., NATURE, vol. 256, 1975, pages 495 - 497
JOURNAL OF MOLECULAR BIOLOGY, vol. 48, 1970, pages 443 - 453
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AOKI, Atsushi et al. (JP)
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