New agents for targeting of IL-13RA2 expressed in primary human and canine brain tumors.
New agents for targeting of IL-13RA2 expressed in primary human and canine brain tumors.
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DOI：
10.1371/journal.pone.0077719
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gibo DM
中科院分区：
文献类型：
--
作者：
Debinski W;Dickinson P;Rossmeisl JH;Robertson J;Gibo DM
白细胞介素13受体α 2（IL-13 RA 2）在绝大多数患有高级别星形细胞瘤（如胶质母细胞瘤）的人类患者中过度表达。狗的自发性星形细胞瘤与人类疾病相似，已被提议作为研究脑肿瘤新治疗策略的转化模型系统。我们已经产生了用于人和犬脑肿瘤中IL-13 RA 2的检测和治疗靶向的试剂。将来自IL-13 RA 2的三个不同区域的肽用作免疫原以产生单克隆抗体，所述肽在人和犬受体之间具有100%序列同一性。还产生了重组犬突变体IL-13（canIL-13.E13K）和基于canIL-13.E13K的细胞毒素。使用人和犬肿瘤标本切片、组织裂解物和建立的细胞系，在蛋白质印迹、免疫组织化学、免疫荧光和细胞结合试验中检查抗体的免疫反应性;检测细胞毒素的特异性细胞杀伤。几种分离的MAb在来自人和犬患者的胶质母细胞瘤的细胞和组织裂解物的蛋白质印迹中对IL-13 RA 2具有免疫反应性。人和犬星形细胞瘤和少突胶质细胞瘤也呈不同程度的IL-13 RA 2阳性。有趣的是，人和犬脑膜瘤也表现出强烈的反应性。使用新产生的MAb，正常人和犬脑样品对IL-13 RA 2几乎呈阴性。MAb 1 E10 B 9独特地作用于组织标本和蛋白质印迹，结合活细胞并在过表达IL-13 RA 2的GBM细胞中内化。犬IL-13.E13K细胞毒素在杀死犬GBM细胞系中是非常有效和特异的。因此，我们已经获得了几种抗IL-13 RA 2的单克隆抗体，其与人和犬受体交叉反应。除了GBM，其他脑肿瘤，如高级别少突胶质细胞瘤、脑膜瘤和犬脉络丛乳头状瘤，似乎以高水平表达受体，因此可能是IL-13 RA 2靶向成像/治疗的合适候选者。犬自发性原发性脑肿瘤是人类肿瘤的一个很好的转化模型。
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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影响因子：
50.3
作者：
Binda E;Visioli A;Giani F;Lamorte G;Copetti M;Pitter KL;Huse JT;Cajola L;Zanetti N;DiMeco F;De Filippis L;Mangiola A;Maira G;Anile C;De Bonis P;Reynolds BA;Pasquale EB;Vescovi AL
通讯作者：
Vescovi AL
影响因子：
5.7
作者：
Debinski, W;Gibo, DM
通讯作者：
Gibo, DM
影响因子：
4.8
作者：
DEBINSKI, W;OBIRI, NI;PURI, RK
通讯作者：
PURI, RK
影响因子：
4.1
作者：
Dickinson, Peter J.;LeCouteur, Richard A.;Bankiewicz, Krystof S.
通讯作者：
Bankiewicz, Krystof S.
DOI：
10.1158/1078-0432.ccr-11-1669
发表时间：
2012-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brown CE;Starr R;Aguilar B;Shami AF;Martinez C;D'Apuzzo M;Barish ME;Forman SJ;Jensen MC
通讯作者：
Jensen MC