دورية أكاديمية
Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer.
| العنوان: | Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer. |
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| المؤلفون: | Koopman LA; Genmab, Utrecht, Netherlands., Terp MG; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark., Zom GG; Genmab, Utrecht, Netherlands., Janmaat ML; Genmab, Utrecht, Netherlands., Jacobsen K; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark., Gresnigt-van den Heuvel E; Genmab, Utrecht, Netherlands., Brandhorst M; Genmab, Utrecht, Netherlands., Forssmann U; Genmab, Utrecht, Netherlands., de Bree F; Genmab, Utrecht, Netherlands., Pencheva N; Genmab, Utrecht, Netherlands., Lingnau A; Genmab, Utrecht, Netherlands., Zipeto MA; Crown Bioscience San Diego, San Diego, California, USA., Parren PW; Genmab, Utrecht, Netherlands.; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands., Breij EC; Genmab, Utrecht, Netherlands., Ditzel HJ; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.; Department of Oncology, Odense University Hospital, Odense, Denmark. |
| المصدر: | JCI insight [JCI Insight] 2019 Nov 01; Vol. 4 (21). Date of Electronic Publication: 2019 Nov 01. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Antineoplastic Agents/*therapeutic use , Carcinoma, Non-Small-Cell Lung/*drug therapy , Immunoconjugates/*therapeutic use , Lung Neoplasms/*drug therapy , Proto-Oncogene Proteins/*immunology , Receptor Protein-Tyrosine Kinases/*immunology, Animals ; Humans ; Mice ; Xenograft Model Antitumor Assays ; Axl Receptor Tyrosine Kinase |
| مستخلص: | Targeted therapies and immunotherapy have shown promise in patients with non-small cell lung cancer (NSCLC). However, the majority of patients fail or become resistant to treatment, emphasizing the need for novel treatments. In this study, we confirm the prognostic value of levels of AXL, a member of the TAM receptor tyrosine kinase family, in NSCLC and demonstrate potent antitumor activity of the AXL-targeting antibody-drug conjugate enapotamab vedotin across different NSCLC subtypes in a mouse clinical trial of human NSCLC. Tumor regression or stasis was observed in 17/61 (28%) of the patient-derived xenograft (PDX) models and was associated with AXL mRNA expression levels. Significant single-agent activity of enapotamab vedotin was validated in vivo in 9 of 10 AXL-expressing NSCLC xenograft models. In a panel of EGFR-mutant NSCLC cell lines rendered resistant to EGFR inhibitors in vitro, we observed de novo or increased AXL protein expression concomitant with enapotamab vedotin-mediated cytotoxicity. Enapotamab vedotin also showed antitumor activity in vivo in 3 EGFR-mutant, EGFR inhibitor-resistant PDX models, including an osimertinib-resistant NSCLC PDX model. In summary, enapotamab vedotin has promising therapeutic potential in NSCLC. The safety and preliminary efficacy of enapotamab vedotin are currently being evaluated in the clinic across multiple solid tumor types, including NSCLC. |
| References: | Int J Cancer. 2015 Mar 1;136(5):E359-86. (PMID: 25220842) Nat Commun. 2019 Jan 16;10(1):259. (PMID: 30651547) N Engl J Med. 2010 Jun 24;362(25):2380-8. (PMID: 20573926) N Engl J Med. 2018 Jan 11;378(2):113-125. (PMID: 29151359) Oncogene. 2013 Jul 18;32(29):3420-31. (PMID: 22890323) Cell. 2007 Dec 14;131(6):1124-36. (PMID: 18083102) Nat Genet. 2012 Jul 01;44(8):852-60. (PMID: 22751098) Int J Clin Exp Pathol. 2014 Sep 15;7(10):6653-61. (PMID: 25400744) Ann Oncol. 2015 Oct;26(10):2073-8. (PMID: 26269204) N Engl J Med. 2018 Jun 14;378(24):2288-2301. (PMID: 29863955) Oncol Rep. 2017 Jun;37(6):3261-3269. (PMID: 28440492) Clin Cancer Res. 2016 Mar 15;22(6):1313-7. (PMID: 26763248) Int J Cancer. 2019 Sep 15;145(6):1609-1624. (PMID: 31162839) Lung Cancer. 2019 Apr;130:149-155. (PMID: 30885336) Anticancer Agents Med Chem. 2018;18(14):2062-2067. (PMID: 30501603) Cancer Discov. 2014 Sep;4(9):1046-61. (PMID: 24893891) Theranostics. 2016 May 24;6(8):1205-19. (PMID: 27279912) Cancer Discov. 2018 Dec;8(12):1529-1539. (PMID: 30257958) Br J Cancer. 2017 Feb 14;116(4):415-423. (PMID: 28072762) Nat Med. 2018 Feb;24(2):203-212. (PMID: 29334371) Clin Lung Cancer. 2014 May;15(3):222-230.e3. (PMID: 24486059) PLoS One. 2013 Dec 18;8(12):e82241. (PMID: 24367507) Cell. 2016 Mar 24;165(1):35-44. (PMID: 26997480) Clin Cancer Res. 2018 Dec 15;24(24):6195-6203. (PMID: 30228210) Int J Cancer. 2005 Aug 10;116(1):36-44. (PMID: 15761868) Nat Rev Cancer. 2014 Dec;14(12):769-85. (PMID: 25568918) EBioMedicine. 2018 Mar;29:112-127. (PMID: 29433983) N Engl J Med. 2009 Sep 3;361(10):958-67. (PMID: 19692684) Oncotarget. 2015 Apr 20;6(11):9206-19. (PMID: 25826078) Nat Commun. 2017 Sep 4;8(1):410. (PMID: 28871105) Cancer Res. 2007 Apr 15;67(8):3878-87. (PMID: 17440102) Lancet Oncol. 2010 Feb;11(2):121-8. (PMID: 20022809) Cancer Sci. 2013 Jul;104(7):904-11. (PMID: 23566288) Oncol Lett. 2018 Mar;15(3):2726-2734. (PMID: 29434997) N Engl J Med. 2005 Feb 24;352(8):786-92. (PMID: 15728811) Br J Cancer. 2018 Jan;118(1):9-16. (PMID: 29319049) Ann Surg Oncol. 2013 Dec;20 Suppl 3:S467-76. (PMID: 23242819) EBioMedicine. 2019 May;43:180-187. (PMID: 31027916) Clin Cancer Res. 2016 Oct 1;22(19):4880-4889. (PMID: 27354471) Cancer Res. 2009 Apr 15;69(8):3256-61. (PMID: 19351834) N Engl J Med. 2018 May 31;378(22):2078-2092. (PMID: 29658856) Clin Cancer Res. 2013 Jan 1;19(1):279-90. (PMID: 23091115) Cancer Cell. 2010 Jan 19;17(1):77-88. (PMID: 20129249) PLoS Med. 2005 Mar;2(3):e73. (PMID: 15737014) Mol Cancer Res. 2019 Feb;17(2):499-507. (PMID: 30463991) Oncol Res. 2016;24(5):295-303. (PMID: 27712586) Oncogene. 2016 Jul 14;35(28):3681-91. (PMID: 26616860) Cancer Res. 2005 Jan 1;65(1):226-35. (PMID: 15665299) Lancet Oncol. 2012 Mar;13(3):239-46. (PMID: 22285168) JAMA Oncol. 2018 Nov 1;4(11):1527-1534. (PMID: 30073261) Nat Commun. 2016 Dec 23;7:13898. (PMID: 28008921) |
| فهرسة مساهمة: | Keywords: Cancer; Drug therapy; Lung cancer; Oncology; Therapeutics |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Immunoconjugates) 0 (Proto-Oncogene Proteins) EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) 0 (Axl Receptor Tyrosine Kinase) |
| تواريخ الأحداث: | Date Created: 20191011 Date Completed: 20201027 Latest Revision: 20221207 |
| رمز التحديث: | 20240513 |
| مُعرف محوري في PubMed: | PMC6948776 |
| DOI: | 10.1172/jci.insight.128199 |
| PMID: | 31600169 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.128199 |