Asunercept (APG101) und CD95

3D Cellular Architecture Modulates Tyrosine Kinase Activity, Thereby Switching CD95-Mediated Apoptosis to Survival
Gülcüler Balta GS, Monzel C, Kleber S, Beaudouin J, Balta E, Kaindl T, Chen S, Gao L, Thiemann M, Wirtz CR, Samstag Y, Tanaka M, Martin-Villalba A. Cell Rep. 2019 Nov 19;29(8):2295-2306.e6. doi: 10.1016/j.celrep.2019.10.054

Longitudinal analysis of quality of life following treatment with Asunercept plus reirradiation versus reirradiation in progressive glioblastoma patients
Wick W, Krendyukov A, Junge K, Höger T, Fricke H. J Neurooncol. 2019 Nov 2. doi: 10.1007/s11060-019-03320-x. [Epub ahead of print]

Asunercept as an innovative therapeutic approach for recurrent glioblastoma and other malignancies
Krendyukov A, Gieffers C. Cancer Manag Res. 2019 Sep 2;11:8095-8100. doi: 10.2147/CMAR.S216675

Translational PBPK Modeling of the Protein Therapeutic and CD95L Inhibitor Asunercept to Develop Dose Recommendations for Its First Use in Pediatric Glioblastoma Patients
Hanke N, Kunz C, Thiemann M, Fricke H, Lehr T. Pharmaceutics. 2019 Apr 1;11(4). pii: E152. doi: 10.3390/pharmaceutics11040152

N2M2 (NOA-20) phase I/II trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed non-MGMT hypermethylated glioblastoma
Wick W, Dettmer S, Berberich A, Kessler T, Karapanagiotou-Schenkel I, Wick A, Winkler F, Pfaff E, Brors B, Debus J, Unterberg A, Bendszus M, Herold-Mende C, Eisenmenger A, von Deimling A, Jones DTW, Pfister SM, Sahm F, Platten M. Neuro Oncol. 2019 Jan 1;21(1):95-105. doi: 10.1093/neuonc/noy161

Inhibition of CD95/CD95L (Fas/FasLg) Signaling with APG101 Prevents Invasion and Enhances Radiation Therapy for Glioblastoma
Blaes J, Thomé CM, Pfenning PN, Rübmann P, Sahm F, Wick A, Bunse T, Schmenger T, Sykora J, von Deimling A, Wiestler B, Merz C, Jugold M, Haberkorn U, Abdollahi A, Debus J, Gieffers C, Kunz C, Bendszus M, Kluge M, Platten M, Fricke H, Wick W, Lemke D. Mol Cancer Res. 2018 May;16(5):767-776. doi: 10.1158/1541-7786.MCR-17-0563

Safety and efficacy of the CD95-ligand inhibitor asunercept in transfusion-dependent patients with low and intermediate risk MDS
Boch T, Luft T, Metzgeroth G, Mossner M, Jann JC, Nowak D, Meir F, Schumann C, Klemmer J, Brendel S, Fricke H, Kunz C, Weiß C, Hofmann WK, Nolte F. Leuk Res. 2018 May;68:62-69. doi: 10.1016/j.leukres.2018.03.007

Peripheral monocytes are functionally altered and invade the CNS in ALS patients
Zondler L, Müller K, Khalaji S, Bliederhäuser C, Ruf WP, Grozdanov V, Thiemann M, Fundel-Clemes K, Freischmidt A, Holzmann K, Strobel B, Weydt P, Witting A, Thal DR, Helferich AM, Hengerer B, Gottschalk KE, Hill O, Kluge M, Ludolph AC, Danzer KM, Weishaupt JH. Acta Neuropathol. 2016 Sep;132(3):391-411. doi: 10.1007/s00401-016-1548-y

CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells
Drachsler M, Kleber S, Mateos A, Volk K, Mohr N, Chen S, Cirovic B, Tüttenberg J, Gieffers C, Sykora J, Wirtz CR, Mueller W, Synowitz M, Martin-Villalba A. Cell Death Dis. 2016 Apr 28;7:e2209. doi: 10.1038/cddis.2016.102

APG101 efficiently rescues erythropoiesis in lower risk myelodysplastic syndromes with severe impairment of hematopoiesis
Raimbault A, Pierre-Eugene C, Rouquette A, Deudon C, Willems L, Chapuis N, Mathis S, Kunz C, Fricke H, Kosmider O, Bardet V, Fontenay M; Groupe Francophone des Myélodysplasies. Oncotarget. 2016 Mar 22;7(12):14898-911. doi: 10.18632/oncotarget.7469

Neutralization of the CD95 ligand by APG101 inhibits invasion of glioma cells in vitro
Merz C, Strecker A, Sykora J, Hill O, Fricke H, Angel P, Gieffers C, Peterziel H. Anticancer Drugs. 2015 Aug;26(7):716-27. doi: 10.1097/CAD.0000000000000237

CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma
Teodorczyk M, Kleber S, Wollny D, Sefrin JP, Aykut B, Mateos A, Herhaus P, Sancho-Martinez I, Hill O, Gieffers C, Sykora J, Weichert W, Eisen C, Trumpp A, Sprick MR, Bergmann F, Welsch T, Martin-Villalba A. Cell Death Differ. 2015 Jul;22(7):1192-202. doi: 10.1038/cdd.2014.217

Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice
Gao L, Brenner D, Llorens-Bobadilla E, Saiz-Castro G, Frank T, Wieghofer P, Hill O, Thiemann M, Karray S, Prinz M, Weishaupt JH, Martin-Villalba A. J Exp Med. 2015 Apr 6;212(4):469-80. doi: 10.1084/jem.20132423

A phase II, randomized, study of weekly APG101+reirradiation versus reirradiation in progressive glioblastoma
Wick W, Fricke H, Junge K, Kobyakov G, Martens T, Heese O, Wiestler B, Schliesser MG, von Deimling A, Pichler J, Vetlova E, Harting I, Debus J, Hartmann C, Kunz C, Platten M, Bendszus M, Combs SE. Clin Cancer Res. 2014 Dec 15;20(24):6304-13. doi: 10.1158/1078-0432.CCR-14-0951-T

Recombinant CD95-Fc (APG101) prevents graft-versus-host disease in mice without disabling antitumor cytotoxicity and T-cell functions
Hartmann N, Messmann JJ, Leithäuser F, Weiswange M, Kluge M, Fricke H, Debatin KM, Strauss G. Blood. 2013 Jan 17;121(3):556-65. doi: 10.1182/blood-2012-04-423392

Pharmacokinetics, pharmacodynamics, safety and tolerability of APG101, a CD95-Fc fusion protein, in healthy volunteers and two glioma patients
Tuettenberg J, Seiz M, Debatin KM, Hollburg W, von Staden M, Thiemann M, Hareng B, Fricke H, Kunz C. Int Immunopharmacol. 2012 Mar 21;13(1):93-100. doi: 10.1016/j.intimp.2012.03.004

CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site
Letellier E, Kumar S, Sancho-Martinez I, Krauth S, Funke-Kaiser A, Laudenklos S, Konecki K, Klussmann S, Corsini NS, Kleber S, Drost N, Neumann A, Lévi-Strauss M, Brors B, Gretz N, Edler L, Fischer C, Hill O, Thiemann M, Biglari B, Karray S, Martin-Villalba A. Immunity. 2010; February 26(32): 240–252. doi: 10.1016/j.immuni.2010.01.011

The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair
Corsini NS, Sancho-Martinez I, Laudenklos S, Glagow D, Kumar S, Letellier E, Koch P, Teodorczyk M, Kleber S, Klussmann S, Wiestler B, Brüstle O, Mueller W, Gieffers C, Hill O, Thiemann M, Seedorf M, Gretz N, Sprengel R, Celikel T, Martin-Villalba A. Cell Stem Cell. 2009 Aug 7;5(2):178-90. doi: 10.1016/j.stem.2009.05.004

Yes and PI3K bind CD95 to signal invasion of glioblastoma
Kleber S, Sancho-Martinez I, Wiestler B, Beisel A, Gieffers C, Hill O, Thiemann M, Mueller W, Sykora J, Kuhn A, Schreglmann N, Letellier E, Zuliani C, Klussmann S, Teodorczyk M, Gröne HJ, Ganten TM, Sültmann H, Tüttenberg J, von Deimling A, Regnier-Vigouroux A, Herold-Mende C, Martin-Villalba A. Cancer Cell. 2008 Mar;13(3):235-48. doi: 10.1016/j.ccr.2008.02.003

 

HERA-Liganden

Concepts for agonistic targeting of CD40 in immuno-oncology
Richards DM, Sefrin JP, Gieffers C, Hill O, Merz C.Hum Vaccin Immunother. 2019 Sep 5:1-11. doi: 10.1080/21645515.2019.1653744

HERA-GITRL activates T cells and promotes anti-tumor efficacy independent of FcγR-binding functionality
Richards DM, Marschall V, Billian-Frey K, Heinonen K, Merz C, Redondo Müller M, Sefrin JP, Schröder M, Sykora J, Fricke H, Hill O, Gieffers C, Thiemann M. J Immunother Cancer. 2019 Jul 19;7(1):191. doi: 10.1186/s40425-019-0671-4

The Hexavalent CD40 Agonist HERA-CD40L Induces T-Cell-mediated Antitumor Immune Response Through Activation of Antigen-presenting Cells
Merz C, Sykora J, Marschall V, Richards DM, Heinonen K, Redondo Müller M, Thiemann M, Schnyder T, Fricke H, Hill O, Gieffers C. J Immunother. 2018 Nov/Dec;41(9):385-398. doi: 10.1097/CJI.0000000000000246

A Single-Chain-Based Hexavalent CD27 Agonist Enhances T Cell Activation and Induces Anti-Tumor Immunity
Thiemann M, Richards DM, Heinonen K, Kluge M, Marschall V, Merz C, Redondo Müller M, Schnyder T, Sefrin JP, Sykora J, Fricke H, Gieffers C, Hill O. Front Oncol. 2018 Sep 19;8:387. doi: 10.3389/fonc.2018.00387

The novel TRAIL-receptor agonist APG350 exerts superior therapeutic activity in pancreatic cancer cells
Legler K, Hauser C, Egberts JH, Willms A, Heneweer C, Boretius S, Röcken C, Glüer CC, Becker T, Kluge M, Hill O, Gieffers C, Fricke H, Kalthoff H, Lemke J, Trauzold A. Cell Death Dis. 2018 May 1;9(5):445. doi: 10.1038/s41419-018-0478-0

hvTRA, a novel TRAIL receptor agonist, induces apoptosis and sustained growth retardation in melanoma
Fleten KG, Flørenes VA, Prasmickaite L, Hill O, Sykora J, Mælandsmo GM, Engesæter B. Cell Death Discov. 2016 Dec 12;2:16081. doi: 10.1038/cddiscovery.2016.81

APG350 induces superior clustering of TRAIL receptors and shows therapeutic antitumor efficacy independent of cross-linking via Fcγ receptors
Gieffers C, Kluge M, Merz C, Sykora J, Thiemann M, Schaal R, Fischer C, Branschädel M, Abhari BA, Hohenberger P, Fulda S, Fricke H, Hill O. Mol Cancer Ther. 2013 Dec;12(12):2735-47. doi: 10.1158/1535-7163.MCT-13-0323