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Sym021, a promising anti-PD1 clinical candidate antibody derived from a new chicken antibody discovery platform.

Gjetting T, Gad M, Fröhlich C, Lindsted T, Melander MC, Bhatia VK, Grandal MM, Dietrich N, Uhlenbrock F, Galler GR, Strandh M, Lantto J, Bouquin T, Horak ID, Kragh M, Pedersen MW, Koefoed K.

MAbs. 2019 May/Jun;11(4):666-680. doi: 10.1080/19420862.2019.1596514. Epub 2019 May 3.


Sym004-induced EGFR elimination is associated with profound anti-tumor activity in EGFRvIII patient-derived glioblastoma models.

Keir ST, Chandramohan V, Hemphill CD, Grandal MM, Melander MC, Pedersen MW, Horak ID, Kragh M, Desjardins A, Friedman HS, Bigner DD.

J Neurooncol. 2018 Jul;138(3):489-498. doi: 10.1007/s11060-018-2832-6. Epub 2018 Mar 21.


Acquired Resistance to a MET Antibody In Vivo Can Be Overcome by the MET Antibody Mixture Sym015.

Pollmann SE, Calvert VS, Rao S, Boca SM, Madhavan S, Horak ID, Kjaer A, Petricoin EF, Kragh M, Poulsen TT.

Mol Cancer Ther. 2018 Jun;17(6):1259-1270. doi: 10.1158/1535-7163.MCT-17-0787. Epub 2018 Mar 15.


Forty-nine gastric cancer cell lines with integrative genomic profiling for development of c-MET inhibitor.

Kim HJ, Kang SK, Kwon WS, Kim TS, Jeong I, Jeung HC, Kragh M, Horak ID, Chung HC, Rha SY.

Int J Cancer. 2018 Jul 1;143(1):151-159. doi: 10.1002/ijc.31304. Epub 2018 Feb 23.


Efficacy of Sym004 in Patients With Metastatic Colorectal Cancer With Acquired Resistance to Anti-EGFR Therapy and Molecularly Selected by Circulating Tumor DNA Analyses: A Phase 2 Randomized Clinical Trial.

Montagut C, Argilés G, Ciardiello F, Poulsen TT, Dienstmann R, Kragh M, Kopetz S, Lindsted T, Ding C, Vidal J, Clausell-Tormos J, Siravegna G, Sánchez-Martín FJ, Koefoed K, Pedersen MW, Grandal MM, Dvorkin M, Wyrwicz L, Rovira A, Cubillo A, Salazar R, Desseigne F, Nadal C, Albanell J, Zagonel V, Siena S, Fumi G, Rospo G, Nadler P, Horak ID, Bardelli A, Tabernero J.

JAMA Oncol. 2018 Apr 12;4(4):e175245. doi: 10.1001/jamaoncol.2017.5245. Epub 2018 Apr 12. Erratum in: JAMA Oncol. 2019 May 1;5(5):745.


An ERBB1-3 Neutralizing Antibody Mixture With High Activity Against Drug-Resistant HER2+ Breast Cancers With ERBB Ligand Overexpression.

Schwarz LJ, Hutchinson KE, Rexer BN, Estrada MV, Gonzalez Ericsson PI, Sanders ME, Dugger TC, Formisano L, Guerrero-Zotano A, Red-Brewer M, Young CD, Lantto J, Pedersen MW, Kragh M, Horak ID, Arteaga CL.

J Natl Cancer Inst. 2017 Nov 1;109(11). doi: 10.1093/jnci/djx065.


Simultaneous Targeting of Two Distinct Epitopes on MET Effectively Inhibits MET- and HGF-Driven Tumor Growth by Multiple Mechanisms.

Grandal MM, Havrylov S, Poulsen TT, Koefoed K, Dahlman A, Galler GR, Conrotto P, Collins S, Eriksen KW, Kaufman D, Woude GFV, Jacobsen HJ, Horak ID, Kragh M, Lantto J, Bouquin T, Park M, Pedersen MW.

Mol Cancer Ther. 2017 Dec;16(12):2780-2791. doi: 10.1158/1535-7163.MCT-17-0374. Epub 2017 Aug 11.


Sym015: A Highly Efficacious Antibody Mixture against MET-Amplified Tumors.

Poulsen TT, Grandal MM, Skartved NJØ, Hald R, Alifrangis L, Koefoed K, Lindsted T, Fröhlich C, Pollmann SE, Eriksen KW, Dahlman A, Jacobsen HJ, Bouquin T, Pedersen MW, Horak ID, Lantto J, Kragh M.

Clin Cancer Res. 2017 Oct 1;23(19):5923-5935. doi: 10.1158/1078-0432.CCR-17-0782. Epub 2017 Jul 5.


Targeting the HER Family with Pan-HER Effectively Overcomes Resistance to Cetuximab.

Iida M, Bahrar H, Brand TM, Pearson HE, Coan JP, Orbuch RA, Flanigan BG, Swick AD, Prabakaran PJ, Lantto J, Horak ID, Kragh M, Salgia R, Kimple RJ, Wheeler DL.

Mol Cancer Ther. 2016 Sep;15(9):2175-86. doi: 10.1158/1535-7163.MCT-16-0012. Epub 2016 Jul 15.


Pan-HER-An antibody mixture targeting EGFR, HER2 and HER3 abrogates preformed and ligand-induced EGFR homo- and heterodimers.

Ellebaek S, Brix S, Grandal M, Lantto J, Horak ID, Kragh M, Poulsen TT.

Int J Cancer. 2016 Nov 1;139(9):2095-105. doi: 10.1002/ijc.30242. Epub 2016 Jul 19.


Cetuximab Resistance in Squamous Carcinomas of the Upper Aerodigestive Tract Is Driven by Receptor Tyrosine Kinase Plasticity: Potential for mAb Mixtures.

Kjær I, Lindsted T, Fröhlich C, Olsen JV, Horak ID, Kragh M, Pedersen MW.

Mol Cancer Ther. 2016 Jul;15(7):1614-26. doi: 10.1158/1535-7163.MCT-15-0565. Epub 2016 May 11.


The First-in-class Anti-EGFR Antibody Mixture Sym004 Overcomes Cetuximab Resistance Mediated by EGFR Extracellular Domain Mutations in Colorectal Cancer.

Sánchez-Martín FJ, Bellosillo B, Gelabert-Baldrich M, Dalmases A, Cañadas I, Vidal J, Martinez A, Argilés G, Siravegna G, Arena S, Koefoed K, Visa L, Arpí O, Horak ID, Iglesias M, Stroh C, Kragh M, Rovira A, Albanell J, Tabernero J, Bardelli A, Montagut C.

Clin Cancer Res. 2016 Jul 1;22(13):3260-7. doi: 10.1158/1078-0432.CCR-15-2400. Epub 2016 Feb 17.


In vivo imaging of therapy response to a novel pan-HER antibody mixture using FDG and FLT positron emission tomography.

Nielsen CH, Jensen MM, Kristensen LK, Dahlman A, Fröhlich C, Jacobsen HJ, Poulsen TT, Lantto J, Horak ID, Kragh M, Kjaer A.

Oncotarget. 2015 Nov 10;6(35):37486-99. doi: 10.18632/oncotarget.6060.


Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer.

Dienstmann R, Patnaik A, Garcia-Carbonero R, Cervantes A, Benavent M, Roselló S, Tops BB, van der Post RS, Argilés G, Skartved NJ, Hansen UH, Hald R, Pedersen MW, Kragh M, Horak ID, Braun S, Van Cutsem E, Tolcher AW, Tabernero J.

Cancer Discov. 2015 Jun;5(6):598-609. doi: 10.1158/2159-8290.CD-14-1432. Epub 2015 May 11.


A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck.

Machiels JP, Specenier P, Krauß J, Dietz A, Kaminsky MC, Lalami Y, Henke M, Keilholz U, Knecht R, Skartved NJ, Horak ID, Pamperin P, Braun S, Gauler TC.

Cancer Chemother Pharmacol. 2015 Jul;76(1):13-20. doi: 10.1007/s00280-015-2761-4. Epub 2015 May 8.


Pan-HER, an Antibody Mixture Simultaneously Targeting EGFR, HER2, and HER3, Effectively Overcomes Tumor Heterogeneity and Plasticity.

Jacobsen HJ, Poulsen TT, Dahlman A, Kjær I, Koefoed K, Sen JW, Weilguny D, Bjerregaard B, Andersen CR, Horak ID, Pedersen MW, Kragh M, Lantto J.

Clin Cancer Res. 2015 Sep 15;21(18):4110-22. doi: 10.1158/1078-0432.CCR-14-3312. Epub 2015 Apr 23.


Targeting Three Distinct HER2 Domains with a Recombinant Antibody Mixture Overcomes Trastuzumab Resistance.

Pedersen MW, Jacobsen HJ, Koefoed K, Dahlman A, Kjær I, Poulsen TT, Meijer PJ, Nielsen LS, Horak ID, Lantto J, Kragh M.

Mol Cancer Ther. 2015 Mar;14(3):669-80. doi: 10.1158/1535-7163.MCT-14-0697. Epub 2015 Jan 22.


Sym004, a novel EGFR antibody mixture, can overcome acquired resistance to cetuximab.

Iida M, Brand TM, Starr MM, Li C, Huppert EJ, Luthar N, Pedersen MW, Horak ID, Kragh M, Wheeler DL.

Neoplasia. 2013 Oct;15(10):1196-206.


Downregulation of HER3 by a novel antisense oligonucleotide, EZN-3920, improves the antitumor activity of EGFR and HER2 tyrosine kinase inhibitors in animal models.

Wu Y, Zhang Y, Wang M, Li Q, Qu Z, Shi V, Kraft P, Kim S, Gao Y, Pak J, Youngster S, Horak ID, Greenberger LM.

Mol Cancer Ther. 2013 Apr;12(4):427-37. doi: 10.1158/1535-7163.MCT-12-0838. Epub 2013 Feb 8.


Reduced expression of the androgen receptor by third generation of antisense shows antitumor activity in models of prostate cancer.

Zhang Y, Castaneda S, Dumble M, Wang M, Mileski M, Qu Z, Kim S, Shi V, Kraft P, Gao Y, Pak J, Sapra P, Bandaru R, Zhao H, Vessella RL, Horak ID, Greenberger LM.

Mol Cancer Ther. 2011 Dec;10(12):2309-19. doi: 10.1158/1535-7163.MCT-11-0329. Epub 2011 Oct 25.


Endogenous knockdown of survivin improves chemotherapeutic response in ALL models.

Morrison DJ, Hogan LE, Condos G, Bhatla T, Germino N, Moskowitz NP, Lee L, Bhojwani D, Horton TM, Belitskaya-Levy I, Greenberger LM, Horak ID, Grupp SA, Teachey DT, Raetz EA, Carroll WL.

Leukemia. 2012 Feb;26(2):271-9. doi: 10.1038/leu.2011.199. Epub 2011 Aug 16.


ErbB3 ablation impairs PI3K/Akt-dependent mammary tumorigenesis.

Cook RS, Garrett JT, Sánchez V, Stanford JC, Young C, Chakrabarty A, Rinehart C, Zhang Y, Wu Y, Greenberger L, Horak ID, Arteaga CL.

Cancer Res. 2011 Jun 1;71(11):3941-51. doi: 10.1158/0008-5472.CAN-10-3775. Epub 2011 Apr 11.


Potent and sustained inhibition of HIF-1α and downstream genes by a polyethyleneglycol-SN38 conjugate, EZN-2208, results in anti-angiogenic effects.

Sapra P, Kraft P, Pastorino F, Ribatti D, Dumble M, Mehlig M, Wang M, Ponzoni M, Greenberger LM, Horak ID.

Angiogenesis. 2011 Sep;14(3):245-53. doi: 10.1007/s10456-011-9209-1. Epub 2011 Mar 31.


Down-modulation of cancer targets using locked nucleic acid (LNA)-based antisense oligonucleotides without transfection.

Zhang Y, Qu Z, Kim S, Shi V, Liao B, Kraft P, Bandaru R, Wu Y, Greenberger LM, Horak ID.

Gene Ther. 2011 Apr;18(4):326-33. doi: 10.1038/gt.2010.133. Epub 2010 Dec 23.


Tumor regression and curability of preclinical neuroblastoma models by PEGylated SN38 (EZN-2208), a novel topoisomerase I inhibitor.

Pastorino F, Loi M, Sapra P, Becherini P, Cilli M, Emionite L, Ribatti D, Greenberger LM, Horak ID, Ponzoni M.

Clin Cancer Res. 2010 Oct 1;16(19):4809-21. doi: 10.1158/1078-0432.CCR-10-1354. Epub 2010 Aug 11.


Down-modulation of survivin expression and inhibition of tumor growth in vivo by EZN-3042, a locked nucleic acid antisense oligonucleotide.

Sapra P, Wang M, Bandaru R, Zhao H, Greenberger LM, Horak ID.

Nucleosides Nucleotides Nucleic Acids. 2010 Feb;29(2):97-112. doi: 10.1080/15257771003597733.


Marked therapeutic efficacy of a novel polyethylene glycol-SN38 conjugate, EZN-2208, in xenograft models of B-cell non-Hodgkin's lymphoma.

Sapra P, Kraft P, Mehlig M, Malaby J, Zhao H, Greenberger LM, Horak ID.

Haematologica. 2009 Oct;94(10):1456-9. doi: 10.3324/haematol.2009.008276.


A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth.

Greenberger LM, Horak ID, Filpula D, Sapra P, Westergaard M, Frydenlund HF, Albaek C, Schrøder H, Ørum H.

Mol Cancer Ther. 2008 Nov;7(11):3598-608. doi: 10.1158/1535-7163.MCT-08-0510. Epub 2008 Oct 30.


Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkers.

Zhao H, Rubio B, Sapra P, Wu D, Reddy P, Sai P, Martinez A, Gao Y, Lozanguiez Y, Longley C, Greenberger LM, Horak ID.

Bioconjug Chem. 2008 Apr;19(4):849-59. doi: 10.1021/bc700333s. Epub 2008 Mar 28.


Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model.

Sapra P, Zhao H, Mehlig M, Malaby J, Kraft P, Longley C, Greenberger LM, Horak ID.

Clin Cancer Res. 2008 Mar 15;14(6):1888-96. doi: 10.1158/1078-0432.CCR-07-4456.


Asparagine synthetase as a causal, predictive biomarker for L-asparaginase activity in ovarian cancer cells.

Lorenzi PL, Reinhold WC, Rudelius M, Gunsior M, Shankavaram U, Bussey KJ, Scherf U, Eichler GS, Martin SE, Chin K, Gray JW, Kohn EC, Horak ID, Von Hoff DD, Raffeld M, Goldsmith PK, Caplen NJ, Weinstein JN.

Mol Cancer Ther. 2006 Nov;5(11):2613-23. Epub 2006 Nov 6.


Therapeutic advantage of pretargeted radioimmunotherapy using a recombinant bispecific antibody in a human colon cancer xenograft.

Karacay H, Brard PY, Sharkey RM, Chang CH, Rossi EA, McBride WJ, Ragland DR, Horak ID, Goldenberg DM.

Clin Cancer Res. 2005 Nov 1;11(21):7879-85.


Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibody.

Sharkey RM, Cardillo TM, Rossi EA, Chang CH, Karacay H, McBride WJ, Hansen HJ, Horak ID, Goldenberg DM.

Nat Med. 2005 Nov;11(11):1250-5. Epub 2005 Oct 30.


Pretargeting of carcinoembryonic antigen-expressing cancers with a trivalent bispecific fusion protein produced in myeloma cells.

Rossi EA, Chang CH, Losman MJ, Sharkey RM, Karacay H, McBride W, Cardillo TM, Hansen HJ, Qu Z, Horak ID, Goldenberg DM.

Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7122s-7129s.


Improving the delivery of radionuclides for imaging and therapy of cancer using pretargeting methods.

Sharkey RM, Karacay H, Cardillo TM, Chang CH, McBride WJ, Rossi EA, Horak ID, Goldenberg DM.

Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7109s-7121s.


Phase II trial of carcinoembryonic antigen radioimmunotherapy with 131I-labetuzumab after salvage resection of colorectal metastases in the liver: five-year safety and efficacy results.

Liersch T, Meller J, Kulle B, Behr TM, Markus P, Langer C, Ghadimi BM, Wegener WA, Kovacs J, Horak ID, Becker H, Goldenberg DM.

J Clin Oncol. 2005 Sep 20;23(27):6763-70.


Effective therapy of human lymphoma xenografts with a novel recombinant ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin.

Chang CH, Sapra P, Vanama SS, Hansen HJ, Horak ID, Goldenberg DM.

Blood. 2005 Dec 15;106(13):4308-14. Epub 2005 Aug 18.


Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys.

Sapra P, Stein R, Pickett J, Qu Z, Govindan SV, Cardillo TM, Hansen HJ, Horak ID, Griffiths GL, Goldenberg DM.

Clin Cancer Res. 2005 Jul 15;11(14):5257-64.


Cancer therapy with radiolabeled and drug/toxin-conjugated antibodies.

Govindan SV, Griffiths GL, Hansen HJ, Horak ID, Goldenberg DM.

Technol Cancer Res Treat. 2005 Aug;4(4):375-91. Review.


Combination antibody therapy with epratuzumab and rituximab in relapsed or refractory non-Hodgkin's lymphoma.

Leonard JP, Coleman M, Ketas J, Ashe M, Fiore JM, Furman RR, Niesvizky R, Shore T, Chadburn A, Horne H, Kovacs J, Ding CL, Wegener WA, Horak ID, Goldenberg DM.

J Clin Oncol. 2005 Aug 1;23(22):5044-51. Epub 2005 Jun 13.


Development of humanized antibodies as cancer therapeutics.

Qu Z, Griffiths GL, Wegener WA, Chang CH, Govindan SV, Horak ID, Hansen HJ, Goldenberg DM.

Methods. 2005 May;36(1):84-95.


Improved therapy of non-Hodgkin's lymphoma xenografts using radionuclides pretargeted with a new anti-CD20 bispecific antibody.

Sharkey RM, Karacay H, Chang CH, McBride WJ, Horak ID, Goldenberg DM.

Leukemia. 2005 Jun;19(6):1064-9.


Advantage of a residualizing iodine radiolabel in the therapy of a colon cancer xenograft targeted with an anticarcinoembryonic antigen monoclonal antibody.

Stein R, Govindan SV, Hayes M, Griffiths GL, Hansen HJ, Horak ID, Goldenberg DM.

Clin Cancer Res. 2005 Apr 1;11(7):2727-34.


Clinical-scale radiolabeling of a humanized anticarcinoembryonic antigen monoclonal antibody, hMN-14, with residualizing 131I for use in radioimmunotherapy.

Govindan SV, Griffiths GL, Stein R, Andrews P, Sharkey RM, Hansen HJ, Horak ID, Goldenberg DM.

J Nucl Med. 2005 Jan;46(1):153-9.


Carcinoembryonic antigen antibody inhibits lung metastasis and augments chemotherapy in a human colonic carcinoma xenograft.

Blumenthal RD, Osorio L, Hayes MK, Horak ID, Hansen HJ, Goldenberg DM.

Cancer Immunol Immunother. 2005 Apr;54(4):315-27. Epub 2004 Dec 11.


Antiproliferative activity of a humanized anti-CD74 monoclonal antibody, hLL1, on B-cell malignancies.

Stein R, Qu Z, Cardillo TM, Chen S, Rosario A, Horak ID, Hansen HJ, Goldenberg DM.

Blood. 2004 Dec 1;104(12):3705-11. Epub 2004 Aug 5.


Preclinical therapy of breast cancer with a radioiodinated humanized anti-EGP-1 monoclonal antibody: advantage of a residualizing iodine radiolabel.

Govindan SV, Stein R, Qu Z, Chen S, Andrews P, Ma H, Hansen HJ, Griffiths GL, Horak ID, Goldenberg DM.

Breast Cancer Res Treat. 2004 Mar;84(2):173-82.


Reagents and methods for PET using bispecific antibody pretargeting and 68Ga-radiolabeled bivalent hapten-peptide-chelate conjugates.

Griffiths GL, Chang CH, McBride WJ, Rossi EA, Sheerin A, Tejada GR, Karacay H, Sharkey RM, Horak ID, Hansen HJ, Goldenberg DM.

J Nucl Med. 2004 Jan;45(1):30-9.

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