دورية أكاديمية
أعرض في EDS

LRRC15 Targeting in Soft-Tissue Sarcomas: Biological and Clinical Implications.

التفاصيل البيبلوغرافية
العنوان: LRRC15 Targeting in Soft-Tissue Sarcomas: Biological and Clinical Implications.
المؤلفون: Ben-Ami E; Sarcoma Division, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Perret R; Department of Pathology, Institut Bergonié, 33000 Bordeaux, France., Huang Y; Sarcoma Division, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Courgeon F; Sarcoma Unit, Institut Bergonié, 33000 Bordeaux, France.; INSERMU1218, 33000 Bordeaux, France., Gokhale PC; Sarcoma Division, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Laroche-Clary A; Sarcoma Unit, Institut Bergonié, 33000 Bordeaux, France.; INSERMU1218, 33000 Bordeaux, France., Eschle BK; Sarcoma Division, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Velasco V; Department of Pathology, Institut Bergonié, 33000 Bordeaux, France., Le Loarer F; Department of Pathology, Institut Bergonié, 33000 Bordeaux, France., Algeo MP; University of Bordeaux, 33400 Talence, France., Purcell J; AbbVie Biotherapeutics, Redwood City, CA 94063, USA., Demetri GD; Sarcoma Division, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02215, USA., Italiano A; Sarcoma Unit, Institut Bergonié, 33000 Bordeaux, France.; INSERMU1218, 33000 Bordeaux, France.; University of Bordeaux, 33400 Talence, France.
المصدر: Cancers [Cancers (Basel)] 2020 Mar 23; Vol. 12 (3). Date of Electronic Publication: 2020 Mar 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مستخلص: Background: LRRC15 is a member of the LRR (leucine-rich repeat) superfamily present on tumor-associated fibroblasts (CAFs) and stromal cells. The expression of LRRC15 is upregulated by the pro-inflammatory cytokine TGFβ. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody-drug conjugate (ADC) designed to target LRRC15, and which has shown significant anti-tumor activity in several tumor models. This is the first focused examination of LRRC15 expression and ABBV-085 activity in soft-tissue sarcomas (STS).
Methods: We analyzed the LRRC15 expression profile by immunohistochemistry in 711 STS cases, covering a broad spectrum of STS histologies and sub-classifications. In vivo experiments were carried out by using LRRC15-positive and LRRC15-negative patient-derived xenograft (PDX) models of STS.
Results: In contrast to patterns observed in epithelial tumors, LRRC15 was expressed not only by stromal cells but also by cancer cells in multiple subsets of STS with significant variations noted between histological subtypes. Overexpression of LRRC15 is positively correlated with grade and independently associated with adverse outcome. ABBV-085 has robust preclinical efficacy against LRRC15 positive STS patient-derived xenograft (PDX) models.
Conclusion: We provide the first preclinical evidence that LRRC15 targeting with an antibody-drug conjugate is a promising strategy in LRRC15-positive STS. ABBV-085 is being evaluated in an ongoing clinical trial in STS and other malignancies.
References: Cancer Res. 2018 Jul 15;78(14):4059-4072. (PMID: 29764866)
Nat Rev Immunol. 2015 Nov;15(11):669-82. (PMID: 26471778)
Cancer. 2011 Mar 1;117(5):1049-54. (PMID: 20945333)
Clin Cancer Res. 2012 Aug 15;18(16):4266-76. (PMID: 22896693)
Clin Cancer Res. 2021 Jul 1;27(13):3556-3566. (PMID: 33820780)
Clin Cancer Res. 2004 Sep 1;10(17):5804-7. (PMID: 15355909)
BMC Med. 2017 Apr 10;15(1):78. (PMID: 28391775)
Lancet Oncol. 2017 Nov;18(11):1493-1501. (PMID: 28988646)
Ther Adv Med Oncol. 2017 Dec;9(12):755-767. (PMID: 29449896)
Mol Cancer Ther. 2017 Jul;16(7):1347-1354. (PMID: 28341790)
Science. 2009 Jun 12;324(5933):1457-61. (PMID: 19460966)
JAMA Oncol. 2018 Jan 01;4(1):93-97. (PMID: 28662235)
Cancer Lett. 2015 Jan 28;356(2 Pt B):721-32. (PMID: 25449434)
فهرسة مساهمة: Keywords: ABBV-085; LRRC15; sarcoma
تواريخ الأحداث: Date Created: 20200327 Latest Revision: 20240328
رمز التحديث: 20240329
مُعرف محوري في PubMed: PMC7140027
DOI: 10.3390/cancers12030757
PMID: 32210091
قاعدة البيانات: MEDLINE
الوصف
تدمد:2072-6694
DOI:10.3390/cancers12030757