Abstract 2488: FGFR4 as a potential therapeutic target for monoclonal antibody based intervention in rhabdomyosarcoma

摘要: Background: Rhabdomyosarcoma (RMS) is most common soft tissue sarcoma in childhood and adolescence. There are two major subtypes of RMS - alveolar (ARMS) embryonal (ERMS). With current treatment modalities the 5 year survival rate patients with metastatic disease only about 30%, thus necessitating development novel targeted therapeutic strategies. Fibroblast Growth Factor Receptor 4 (FGFR4) highly differentially expressed gene activating mutations FGFR4 associated increase metastasis. We hypothesize that can be exploited as a potential target RMS. Monoclonal antibodies (mAbs) against specific cancer cell surface antigens, have gained importance agents other types. Therefore, mAbs may developed either alone or conjugated chemotherapeutic agent for Methods: 15 mouse, rabbit human origin. The immunogen extracellular domain (ECD), while FGFR4-Fc chimeric protein hFGFR4 transfected cells were used mouse produced using hybridoma technology. Using recombinant DNA technology, immunoglobulin library was selected ECD to derive anti-FGFR4 mAbs. All purified affinity chromatography reactivity confirmed by ELISA. These tested their ability bind internalization mAb bound (upon incubation at 37°C) flow cytometry lines. To further characterize these we performed immunohistochemistry (IHC) on microarrays (TMA) normal tissue, xenografts lines, primary tumor from patients. Finally, select candidate agent, appropriate secondary antibody-drug conjugate (ADC) based cytotoxic assay. Results: observed both ARMS ERMS level expression variable subtypes. Internalization assays demonstrated internalized Analysis IHC TMAs suggests considerably higher compared tissue. Based findings, currently screening elicit response conjunction ADC. Conclusion: results suggest intervention High cancers such prostate, melanoma, lung, breast, colorectal, gastric use derivatives cancers. Citation Format: Sivasubramanian Baskar, Nityashree Shivaprasad, Zhongyu Zhu, Dimiter Dimitrov, Mhairi Sigrist, Poul Sorensen, Marielle Yohe, John Shern, Maris, Crystal Mackall, Javed Khan. monoclonal antibody rhabdomyosarcoma. [abstract]. In: Proceedings 106th Annual Meeting American Association Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Res 2015;75(15 Suppl):Abstract nr 2488. doi:10.1158/1538-7445.AM2015-2488