Abstract 2866: Surfaceome profiling in osteosarcoma: Identification of the candidate immunotherapeutic target
Year: 2019
Type: conference-abstract
Abstract: Osteosarcoma (OS) is the most common primary malignant bone tumor in pediatric patients. Current developments in targeted therapeutic strategies show potential clinical implications in cancer treatments. However, immunotherapies such as antibody-drug conjugates (ADCs) or CAR-T cell therapy have not been sufficiently studied in OS because of the lack of tumor-specific target. In this study, we developed a multi-step RNA-seq based pipeline. First, we did RNA sequencing for our OS PDX models and 17 patient-derived OS cell lines. The results are then pooled with the RNQ-seq data from 111 OS patient via the Therapeutically Applicable Research to Generate Effective Treatments project (TARGET). All these tumor data are subsequently compared with normal tissue RNA-sequencing data from NIH Genotype-Tissue Expression (GTEx) database. The significantly differentially expressed genes (log fold change tumor versus normal >1 for each tissue, p < 0.01) are selected. We further filtered this gene list by cell surface protein prediction based on Gene Ontology, the TransMembrane prediction using hidden Markov models (TMHMM), and glycosylphosphatidylinositol (GPI)-anchored protein annotations. Based on the transcriptomic result, ranks of differentially expressed genes were generated. CD276, LCLAT1, and OR8B12 are the surface markers with high ranks. To validate the transcriptomic results, we prepared surface protein extraction of the PDX models and patient-derived OS cell lines. We are profiling these surface proteins by proteomic mass spectrometry. Further validation for the expression level and location of these markers are underway. Our current finding is not previously reported in OS. The results warrant further development of ADC and car-T cell therapy.Note: This abstract was not presented at the meeting.Citation Format: Yifei Wang, Zhongting Zhang, Sankaranarayanan Kannan, Wendong Zhang, Michael Roth, Jonathan B. Gill, Zhaohui Xu, Xiangjun Tian, Jing Wang, Richard Gorlick. Surfaceome profiling in osteosarcoma: Identification of the candidate immunotherapeutic target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2866.
Source: Tumor Biology
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,500
OpenAlex ID: W2953426156