L-aptamers – Aptarion

Combined inhibition of CXCL12 and PD-1 in MSS colorectal and pancreatic cancer: modulation of the microenvironment and clinical effects.

Suarez-Carmona M, Williams A, Schreiber J, Hohmann N, Pruefer U, Krauss J, Jäger D, Frömming A, Beyer D, Eulberg D, Jungelius JU, Baumann M, Mangasarian A, Halama N. J Immunother Cancer. 2021 Oct;9(10):e002505. doi: 10.1136/jitc-2021-002505. PMID: 34607895 Free PMC article.

CCL2/MCP-1 and CXCL12/SDF-1 blockade by L-Aptamers improve pancreatic islet engraftment and survival in mouse.

Citro A, Pellegrini S, Dugnani E, Eulberg D, Klussmann S, Piemonti L. Am J Transplant. 2019 Nov;19(11):3131-3138. doi: 10.1111/ajt.15518. Epub 2019 Jul 18. PMID: 31267721

Olaptesed pegol (NOX-A12) with bendamustine and rituximab: a phase IIa study in patients with relapsed/refractory chronic lymphocytic leukemia.

Steurer M, Montillo M, Scarfò L, Mauro FR, Andel J, Wildner S, Trentin L, Janssens A, Burgstaller S, Frömming A, Dümmler T, Riecke K, Baumann M, Beyer D, Vauléon S, Ghia P, Foà R, Caligaris-Cappio F, Gobbi M. Haematologica. 2019 Oct;104(10):2053-2060. doi: 10.3324/haematol.2018.205930. Epub 2019 May 16. PMID: 31097627 Free PMC article. Clinical Trial.

Dynamic cellular phynotyping defines specific mobilization mechanisms of human hematopoietic stem and progenitor cells induced by SDF1α versus synthetic agents.

Monzel C, Becker AS, Saffrich R, Wuchter P, Eckstein V, Ho AD, Tanaka M. Sci Rep. 2018 Jan 30;8(1):1841. doi: 10.1038/s41598-018-19557-x. PMID: 29382856 Free PMC article.

Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus.

Fischer MJM, Schmidt J, Koulchitsky S, Klussmann S, Vater A, Messlinger K. J Headache Pain. 2018 Jan 15;19(1):3. doi: 10.1186/s10194-018-0832-8. PMID: 29335794 Free PMC article.

Inhibition of SDF-1-induced migration of oncogene-driven myeloid leukemia by the L-RNA aptamer (Spiegelmer), NOX-A12, and potentiation of tyrosine kinase inhibition.

Weisberg EL, Sattler M, Azab AK, Eulberg D, Kruschinski A, Manley PW, Stone R, Griffin JD. Oncotarget. 2017 Nov 6;8(66):109973-109984. doi: 10.18632/oncotarget.22409. eCollection 2017 Dec 15. PMID: 29299123 Free PMC article.

Increasing Tumor-Infiltrating T Cells through Inhibition of CXCL12 with NOX-A12 Synergizes with PD-1 Blockade.

Zboralski D, Hoehlig K, Eulberg D, Frömming A, Vater A. Cancer Immunol Res. 2017 Nov;5(11):950-956. doi: 10.1158/2326-6066.CIR-16-0303. Epub 2017 Sep 28. PMID: 28963140

Systemic Monocyte Chemotactic Protein-1 Inhibition Modifies Renal Macrophages and Restores Glomerular Endothelial Glycocalyx and Barrier Function in Diabetic Nephropathy.

Boels MGS, Koudijs A, Avramut MC, Sol WMPJ, Wang G, van Oeveren-Rietdijk AM, van Zonneveld AJ, de Boer HC, van der Vlag J, van Kooten C, Eulberg D, van den Berg BM, IJpelaar DHT, Rabelink TJ. Am J Pathol. 2017 Nov;187(11):2430-2440. doi: 10.1016/j.ajpath.2017.07.020. Epub 2017 Aug 22. PMID: 28837800 Free article.

Olaptesed pegol, an anti-CXCL12/SDF-1 Spiegelmer, alone and with bortezomib-dexamethasone in relapsed/refractory multiple myeloma: a Phase IIa Study.

Ludwig H, Weisel K, Petrucci MT, Leleu X, Cafro AM, Garderet L, Leitgeb C, Foa R, Greil R, Yakoub-Agha I, Zboralski D, Vauléon S, Dümmler T, Beyer D, Kruschinski A, Riecke K, Baumann M, Engelhardt M. Leukemia. 2017 Apr;31(4):997-1000. doi: 10.1038/leu.2017.5. Epub 2017 Jan 11.

C-C motif-ligand 2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria.

Menne J, Eulberg D, Beyer D, Baumann M, Saudek F, Valkusz Z, Więcek A, Haller H; Emapticap Study Group. Nephrol Dial Transplant. 2017 Feb 1;32(2):307-315. doi: 10.1093/ndt/gfv459. PMID: 28186566 Free PMC article. Clinical Trial.

SDF-1 Blockade Enhances Anti-VEGF Therapy of Glioblastoma and Can Be Monitored by MRI.

Deng L, Stafford JH, Liu SC, Chernikova SB, Merchant M, Recht L, Martin Brown J. Neoplasia. 2017 Jan;19(1):1-7. doi: 10.1016/j.neo.2016.11.010. Epub 2016 Dec 7. PMID: 27940247 Free PMC article.

Dual blockade of the pro-inflammatory chemokine CCL2 and the homeostatic chemokine CXCL12 is as effective as high dose cyclophosphamide in murine proliferative lupus nephritis.

Devarapu SK, Kumar Vr S, Rupanagudi KV, Kulkarni OP, Eulberg D, Klussmann S, Anders HJ. Clin Immunol. 2016 Aug;169:139-147. doi: 10.1016/j.clim.2016.07.003. Epub 2016 Jul 5. PMID: 27392463

Safety, pharmacokinetics and pharmacodynamics of the anti-hepcidin Spiegelmer lexaptepid pegol in healthy subjects.

Boyce M, Warrington S, Cortezi B, Zöllner S, Vauléon S, Swinkels DW, Summo L, Schwoebel F, Riecke K. Br J Pharmacol. 2016 May;173(10):1580-8. doi: 10.1111/bph.13433. Epub 2016 Apr 8. PMID: 26773325 Free PMC article. Clinical Trial.

A novel CGRP-neutralizing Spiegelmer attenuates neurogenic plasma protein extravasation.

Hoehlig K, Johnson KW, Pryazhnikov E, Maasch C, Clemens-Smith A, Purschke WG, Vauléon S, Buchner K, Jarosch F, Khiroug L, Vater A, Klussmann S. Br J Pharmacol. 2015 Jun;172(12):3086-98. doi: 10.1111/bph.13110. Epub 2015 Mar 27. PMID: 25659966 Free PMC article.

CXCL12-induced VLA-4 activation is impaired in trisomy 12 chronic lymphocytic leukemia cells: a role for CCL21.

Ganghammer S, Hutterer E, Hinterseer E, Brachtl G, Asslaber D, Krenn PW, Girbl T, Berghammer P, Geisberger R, Egle A, Zucchetto A, Kruschinski A, Gattei V, Chigaev A, Greil R, Hartmann TN. Oncotarget. 2015 May 20;6(14):12048-60. doi: 10.18632/oncotarget.3660. PMID: 25895128 Free PMC article.

Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2.

Oberthür D, Achenbach J, Gabdulkhakov A, Buchner K, Maasch C, Falke S, Rehders D, Klussmann S, Betzel C. Nat Commun. 2015 Apr 22;6:6923. doi: 10.1038/ncomms7923. PMID: 25901662 Free PMC article.

Neonatal ghrelin programs development of hypothalamic feeding circuits.

Steculorum SM, Collden G, Coupe B, Croizier S, Lockie S, Andrews ZB, Jarosch F, Klussmann S, Bouret SG. J Clin Invest. 2015 Feb;125(2):846-58. doi: 10.1172/JCI73688. Epub 2015 Jan 20. PMID: 25607843 Free PMC article.

Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans.

van Eijk LT, John AS, Schwoebel F, Summo L, Vauléon S, Zöllner S, Laarakkers CM, Kox M, van der Hoeven JG, Swinkels DW, Riecke K, Pickkers P. Blood. 2014 Oct 23;124(17):2643-6. doi: 10.1182/blood-2014-03-559484. Epub 2014 Aug 27. PMID: 25163699 Free PMC article. Clinical Trial.

Identification and characterization of a mirror-image oligonucleotide that binds and neutralizes sphingosine 1-phosphate, a central mediator of angiogenesis.

Purschke WG, Hoehlig K, Buchner K, Zboralski D, Schwoebel F, Vater A, Klussmann S. Biochem J. 2014 Aug 15;462(1):153-62. doi: 10.1042/BJ20131422. PMID: 24832383 Free PMC article

SDF-1 inhibition targets the bone marrow niche for cancer therapy.

Roccaro AM, Sacco A, Purschke WG, Moschetta M, Buchner K, Maasch C, Zboralski D, Zöllner S, Vonhoff S, Mishima Y, Maiso P, Reagan MR, Lonardi S, Ungari M, Facchetti F, Eulberg D, Kruschinski A, Vater A, Rossi G, Klussmann S, Ghobrial IM. Cell Rep. 2014 Oct 9;9(1):118-128. doi: 10.1016/j.celrep.2014.08.042. Epub 2014 Sep 25. PMID: 25263552 Free PMC article.

NOX-A12: mobilizing CLL away from home.

Marasca R, Maffei R. Blood. 2014 Feb 13;123(7):952-3. doi: 10.1182/blood-2013-12-542480. PMID: 24526776 No abstract available.

Blockade of SDF-1 after irradiation inhibits tumor recurrences of autochthonous brain tumors in rats.

Liu SC, Alomran R, Chernikova SB, Lartey F, Stafford J, Jang T, Merchant M, Zboralski D, Zöllner S, Kruschinski A, Klussmann S, Recht L, Brown JM. Neuro Oncol. 2014 Jan;16(1):21-8. doi: 10.1093/neuonc/not149. Epub 2013 Dec 10. PMID: 24335554 Free PMC article.

The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility and causes chemosensitization.

Hoellenriegel J, Zboralski D, Maasch C, Rosin NY, Wierda WG, Keating MJ, Kruschinski A, Burger JA. Blood. 2014 Feb 13;123(7):1032-9. doi: 10.1182/blood-2013-03-493924. Epub 2013 Nov 25. PMID: 24277076 Free PMC article.

Bioactive lipids S1P and C1P are prometastatic factors in human rhabdomyosarcoma, and their tissue levels increase in response to radio/chemotherapy.

Schneider G, Bryndza E, Abdel-Latif A, Ratajczak J, Maj M, Tarnowski M, Klyachkin YM, Houghton P, Morris AJ, Vater A, Klussmann S, Kucia M, Ratajczak MZ. Mol Cancer Res. 2013 Jul;11(7):793-807. doi: 10.1158/1541-7786.MCR-12-0600. Epub 2013 Apr 24. PMID: 23615526 Free PMC article.

A mixed mirror-image DNA/RNA aptamer inhibits glucagon and acutely improves glucose tolerance in models of type 1 and type 2 diabetes.

Vater A, Sell S, Kaczmarek P, Maasch C, Buchner K, Pruszynska-Oszmalek E, Kolodziejski P, Purschke WG, Nowak KW, Strowski MZ, Klussmann S. J Biol Chem. 2013 Jul 19;288(29):21136-21147. doi: 10.1074/jbc.M112.444414. Epub 2013 Jun 6. PMID: 23744070 Free PMC article.

Hematopoietic stem and progenitor cell mobilization in mice and humans by a first-in-class mirror-image oligonucleotide inhibitor of CXCL12.

Vater A, Sahlmann J, Kröger N, Zöllner S, Lioznov M, Maasch C, Buchner K, Vossmeyer D, Schwoebel F, Purschke WG, Vonhoff S, Kruschinski A, Hübel K, Humphrey M, Klussmann S, Fliegert F. Clin Pharmacol Ther. 2013 Jul;94(1):150-7. doi: 10.1038/clpt.2013.58. Epub 2013 Mar 19. PMID: 23588307

The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys.

Schwoebel F, van Eijk LT, Zboralski D, Sell S, Buchner K, Maasch C, Purschke WG, Humphrey M, Zöllner S, Eulberg D, Morich F, Pickkers P, Klussmann S. Blood. 2013 Mar 21;121(12):2311-5. doi: 10.1182/blood-2012-09-456756. Epub 2013 Jan 24. PMID: 23349391 Free PMC article.

Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury.

Baeck C, Wehr A, Karlmark KR, Heymann F, Vucur M, Gassler N, Huss S, Klussmann S, Eulberg D, Luedde T, Trautwein C, Tacke F. Gut. 2012 Mar;61(3):416-26. doi: 10.1136/gutjnl-2011-300304. Epub 2011 Aug 3. PMID: 21813474

Dual blockade of the homeostatic chemokine CXCL12 and the proinflammatory chemokine CCL2 has additive protective effects on diabetic kidney disease.

Darisipudi MN, Kulkarni OP, Sayyed SG, Ryu M, Migliorini A, Sagrinati C, Parente E, Vater A, Eulberg D, Klussmann S, Romagnani P, Anders HJ. Am J Pathol. 2011 Jul;179(1):116-24. doi: 10.1016/j.ajpath.2011.03.004. Epub 2011 Apr 30. PMID: 21703397 Free PMC article.

Polyetheylenimine-polyplexes of Spiegelmer NOX-A50 directed against intracellular high mobility group protein A1 (HMGA1) reduce tumor growth in vivo.

Maasch C, Vater A, Buchner K, Purschke WG, Eulberg D, Vonhoff S, Klussmann S. J Biol Chem. 2010 Dec 17;285(51):40012-8. doi: 10.1074/jbc.M110.178533. Epub 2010 Oct 20. PMID: 20961861 Free PMC article.

Podocytes produce homeostatic chemokine stromal cell-derived factor-1/CXCL12, which contributes to glomerulosclerosis, podocyte loss and albuminuria in a mouse model of type 2 diabetes .

Sayyed SG, Hägele H, Kulkarni OP, Endlich K, Segerer S, Eulberg D, Klussmann S, Anders HJ. Diabetologia. 2009 Nov;52(11):2445-54. doi: 10.1007/s00125-009-1493-6. Epub 2009 Aug 26. PMID: 19707743

Ccl2/Mcp-1 blockade reduces glomerular and interstitial macrophages but does not ameliorate renal pathology in collagen4A3-deficient mice with autosomal recessive Alport nephropathy.

Clauss S, Gross O, Kulkarni O, Avila-Ferrufino A, Radomska E, Segerer S, Eulberg D, Klussmann S, Anders HJ. J Pathol. 2009 May;218(1):40-7. doi: 10.1002/path.2505. PMID: 19156777

Anti-Ccl2 Spiegelmer permits 75% dose reduction of cyclophosphamide to control diffuse proliferative lupus nephritis and pneumonitis in MRL-Fas(lpr) mice.

Kulkarni O, Eulberg D, Selve N, Zöllner S, Allam R, Pawar RD, Pfeiffer S, Segerer S, Klussmann S, Anders HJ. J Pharmacol Exp Ther. 2009 Feb;328(2):371-7. doi: 10.1124/jpet.108.142711. Epub 2008 Nov 7. PMID: 18997060

Late onset of Ccl2 blockade with the Spiegelmer mNOX-E36-3’PEG prevents glomerulosclerosis and improves glomerular filtration rate in db/db mice.

Ninichuk V, Clauss S, Kulkarni O, Schmid H, Segerer S, Radomska E, Eulberg D, Buchner K, Selve N, Klussmann S, Anders HJ. Am J Pathol. 2008 Mar;172(3):628-37. doi: 10.2353/ajpath.2008.070601. Epub 2008 Feb 7. PMID: 18258851 Free PMC article.

Spiegelmer inhibition of CCL2/MCP-1 ameliorates lupus nephritis in MRL-(Fas)lpr mice.

Kulkarni O, Pawar RD, Purschke W, Eulberg D, Selve N, Buchner K, Ninichuk V, Segerer S, Vielhauer V, Klussmann S, Anders HJ. J Am Soc Nephrol. 2007 Aug;18(8):2350-8. doi: 10.1681/ASN.2006121348. Epub 2007 Jul 11. PMID: 17625118 Free article.

Inhibition of stimulated meningeal blood flow by a calcitonin gene-related peptide binding mirror-image RNA oligonucleotide.

Denekas T, Tröltzsch M, Vater A, Klussmann S, Messlinger K. Br J Pharmacol. 2006 Jun;148(4):536-43. doi: 10.1038/sj.bjp.0706742. Epub 2006 Apr 24. PMID: 16633354 Free PMC article.

Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats.

Kobelt P, Helmling S, Stengel A, Wlotzka B, Andresen V, Klapp BF, Wiedenmann B, Klussmann S, Mönnikes H. Gut. 2006 Jun;55(6):788-92. doi: 10.1136/gut.2004.061010. Epub 2005 Jun 30. PMID: 15994217 Free PMC article.

An L-RNA-based aquaretic agent that inhibits vasopressin in vivo.

Purschke WG, Eulberg D, Buchner K, Vonhoff S, Klussmann S. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5173-8. doi: 10.1073/pnas.0509663103. Epub 2006 Mar 17. PMID: 16547136 Free PMC article.

Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer.

Helmling S, Maasch C, Eulberg D, Buchner K, Schröder W, Lange C, Vonhoff S, Wlotzka B, Tschöp MH, Rosewicz S, Klussmann S. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13174-9. doi: 10.1073/pnas.0404175101. Epub 2004 Aug 25. PMID: 15329412 Free PMC article.

Short bioactive Spiegelmers to migraine-associated calcitonin gene-related peptide rapidly identified by a novel approach: tailored-SELEX.

Vater A, Jarosch F, Buchner K, Klussmann S. Nucleic Acids Res. 2003 Nov 1;31(21):e130. doi: 10.1093/nar/gng130. PMID: 14576330 Free PMC article.