دورية أكاديمية
أعرض في EDS

New agents for targeting of IL-13RA2 expressed in primary human and canine brain tumors.

التفاصيل البيبلوغرافية
العنوان: New agents for targeting of IL-13RA2 expressed in primary human and canine brain tumors.
المؤلفون: Debinski W; The Brain Tumor Center of Excellence, Thomas K. Hearn Brain Tumor Research Center, Departments of Neurosurgery, Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America., Dickinson P, Rossmeisl JH, Robertson J, Gibo DM
المصدر: PloS one [PLoS One] 2013 Oct 16; Vol. 8 (10), pp. e77719. Date of Electronic Publication: 2013 Oct 16 (Print Publication: 2013).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Antibodies, Monoclonal/*therapeutic use , Brain Neoplasms/*drug therapy , Brain Neoplasms/*metabolism , Interleukin-13 Receptor alpha2 Subunit/*metabolism, Animals ; Blotting, Western ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dogs ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Humans ; Immunoprecipitation ; Interleukin-13 Receptor alpha2 Subunit/antagonists & inhibitors ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured
مستخلص: Interleukin 13 receptor alpha 2 (IL-13RA2) is over-expressed in a vast majority of human patients with high-grade astrocytomas like glioblastoma. Spontaneous astrocytomas in dogs resemble human disease and have been proposed as translational model system for investigation of novel therapeutic strategies for brain tumors. We have generated reagents for both detection and therapeutic targeting of IL-13RA2 in human and canine brain tumors. Peptides from three different regions of IL-13RA2 with 100% sequence identity between human and canine receptors were used as immunogens for generation of monoclonal antibodies. Recombinant canine mutant IL-13 (canIL-13.E13K) and canIL-13.E13K based cytotoxin were also produced. The antibodies were examined for their immunoreactivities in western blots, immunohistochemistry, immunofluorescence and cell binding assays using human and canine tumor specimen sections, tissue lysates and established cell lines; the cytotoxin was tested for specific cell killing. Several isolated MAbs were immunoreactive to IL-13RA2 in western blots of cell and tissue lysates from glioblastomas from both human and canine patients. Human and canine astrocytomas and oligodendrogliomas were also positive for IL-13RA2 to various degrees. Interestingly, both human and canine meningiomas also exhibited strong reactivity. Normal human and canine brain samples were virtually negative for IL-13RA2 using the newly generated MAbs. MAb 1E10B9 uniquely worked on tissue specimens and western blots, bound live cells and was internalized in GBM cells over-expressing IL-13RA2. The canIL-13.E13K cytotoxin was very potent and specific in killing canine GBM cell lines. Thus, we have obtained several monoclonal antibodies against IL-13RA2 cross-reacting with human and canine receptors. In addition to GBM, other brain tumors, such as high grade oligodendrogliomas, meningiomas and canine choroid plexus papillomas, appear to express the receptor at high levels and thus may be appropriate candidates for IL-13RA2-targeted imaging/therapies. Canine spontaneous primary brain tumors represent an excellent translational model for human counterparts.
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معلومات مُعتمدة: R01 CA74145 United States CA NCI NIH HHS; P30 CA093373 United States CA NCI NIH HHS; CA139099 United States CA NCI NIH HHS; P30 CA012197 United States CA NCI NIH HHS; R01 CA074145 United States CA NCI NIH HHS; R01 CA139099 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Antibodies, Monoclonal)
0 (Interleukin-13 Receptor alpha2 Subunit)
تواريخ الأحداث: Date Created: 20131023 Date Completed: 20140605 Latest Revision: 20240326
رمز التحديث: 20240326
مُعرف محوري في PubMed: PMC3797726
DOI: 10.1371/journal.pone.0077719
PMID: 24147065
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0077719