Abstract 1772: PDL192, a humanized anti-Tweak receptor monoclonal antibody, mediates antitumor effects in primary human breast carcinoma xenografts
| العنوان: | Abstract 1772: PDL192, a humanized anti-Tweak receptor monoclonal antibody, mediates antitumor effects in primary human breast carcinoma xenografts |
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| المؤلفون: | Didier Decaudin, Debra Chao, Anne Vincent-Salomon, André Nicolas, Ludmilla de Plater, C. Elbaz, Daniel E. H. Afar, Ahmed Dahmani, Patricia Culp, Véronique Diéras, Franck Assayag, Eléonore Gravier |
| المصدر: | Cancer Research. 71:1772-1772 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Cancer Research, Pathology, medicine.medical_specialty, Cyclophosphamide, medicine.drug_class, business.industry, Estrogen receptor, Cancer, Monoclonal antibody, medicine.disease, Oncology, In vivo, medicine, Cancer research, Carcinoma, Immunohistochemistry, Doxorubicin, business, medicine.drug |
| الوصف: | Background: PDL192 is a humanized IgG1 monoclonal antibody that binds the human TWEAK receptor (TweakR). TweakR, a member of the TNFR (Tumor Necrosis Factor Receptor) superfamily, is overexpressed in several human cancers including breast cancer (BC). In BC, it may also play a role in the invasive and metastatic potential of the disease (Willis et al, Mol Cancer Res 2008). In TweakR-expressing cancer cell lines or mouse xenograft models, PDL192 has a potent antitumor effect (Culp et al., CCR 2010). All these data therefore suggest that anti-TweakR targeting could be a promising new therapeutic approach for human BC patients. Material and methods: TweakR expression was assessed by IHC (immunohistochemistry) on 3 Tissue-Micro-Array (TMA) banks of BC samples (basal-like, ERBB2, and luminal A/B), and 25 primary human BC xenografts (HBCx). The cut-off of positivity was defined as at least 25% cells with membraneous or cytoplasmic staining or by a combined score of percentage of positive staining cells x intensity > 50. The in vivo antitumor effect of PDL192 was then assessed on 7 TweakR-positive models (10 mg/kg thrice a week for 3 weeks by intraperitoneal route) in which one in combination with chemotherapy as maintenance therapy, as previsouly reported (Marangoni et al., BJC 2009). Results: TMA analyses showed that TweakR was expressed in 16/37 basal like BC (43%), 23/37 ERBB2-positive BC (62%), and 38/71 luminal BC (54%). A high TweakR expression was correlated with double estrogen receptor- and Her2-positive tumors. Moreover, 13/25 xenografts have been found to be TweakR-positive (52%). Nine human BC models have been treated with PDL192, with 4 models (44%) showing a tumor growth inhibition (TGI) ranging between 59% and 91%. No correlation has been observed between TweakR expression and in vivo TGI. Moreover, when PDL192 was administered in complete remission after chemotherapy (doxorubicin + cyclophosphamide), we observed a highly significant delay of relapse greater than 2 months. Conclusions: TweakR is expressed in 77/145 human BC samples (53%). In in vivo experiments, PDL192 showed potent TGI in 4/9 models, and significantly delayed tumor relapses after chemotherapy-induced complete remission. All these data therefore support the use of anti-TWEAK receptor monoclonal antibodies in the treatment of TweakR-positive BC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1772. doi:10.1158/1538-7445.AM2011-1772 |
| تدمد: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2011-1772 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::fc5a7ccaf909a8308a2d8997d9aba7f0 https://doi.org/10.1158/1538-7445.am2011-1772 |
| رقم الانضمام: | edsair.doi...........fc5a7ccaf909a8308a2d8997d9aba7f0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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| DOI: | 10.1158/1538-7445.am2011-1772 |