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P. Yang
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-089 - Predictive Value of AEG-1 Expression on Tumor Response by Liquid Biopsy in NSCLC Patients Treated with Chemotherapy (ID 5679)
14:30 - 14:30 | Author(s): P. Yang
- Abstract
Background:
AEG‑1 is important in the aggressiveness of NSCLC and also contributes to induce chemoresistance in treatment of NSCLC. In this study, we will assess the predictive and prognostic values of AEG-1 expression on tumor response and survival according to mRNA concentration by liquid biopsy in NSCLC patients treated with chemotherapy.
Methods:
Patients were diagnosed with a advanced NSCLC (stage IIIB and IV). Patients were enrolled to be treated by chemotherapy as first-line treatment or for metastatic or recurrent disease with Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. All patients underwent blood sampling before any cancer treatment and at first response evaluation. Response to chemotherapy was assessed using RECIST criteria. mRNA was extracted from plasma samples using the QIAamp Circulating Nucleic Acid Kit (Qiagen, Valencia, CA, USA) and quantification of mRNA was performed by real-time PCR (ABI 7900) with SYBR GREEN reagent expression assay for AEG-1.
Results:
A total of 12 patients (9 male and 3 female) with advanced NSCLC received platinum based doublets chemotherapy. Chemotherapy regimens included 8 cisplatin and 4 carboplatin with 5 pemetrexed, 4 paclitaxel, 2 gemcitabine and 1 vinorelbine. 7 of 12 (58.3%) were adenocarcinoma. The initial response rate of chemotherapy included 6 partial responses, 1 stable disease and 5 progressive disease. The expression level of AEG-1 in patients with disease progression after chemotherapy increased significantly compared with the expression level at pre-chemotherapy (AEG-1, relative quantification of mRNA, post-progression, range: 2.14 - 8.61, p = 0.035). In the group of patients with responsive chemotherapy, the mRNA expression level of AEG-1 was not increased compared to the baseline expression (Figure 1). Figure 1
Conclusion:
This result suggests that mRNA concentration of AEG-1 from liquid biopsy could be a predictive biomarker of tumor response. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-090 - A CTLA-4 Antagonizing DNA Aptamer with Anti-Tumor Effect (ID 6008)
14:30 - 14:30 | Author(s): P. Yang
- Abstract
Background:
The discovery of cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade and its successful clinical translation has revolutionized the concept of cancer immunotherapy. Although immunecheckpoint-targeting antibody has shown impressive results in a diverse array of cancers, their cell-based manufacturing process influences production capacity and cause variation between batches. Aptamers are synthetic DNA or RNA oligonucleotides that encompass antibody-mimicking functions. With its chemically synthetic nature, aptamer can be produced in large scale with controllable batch variations and lower manufacturing cost.
Methods:
Here, we report the development of a CTLA-4 antagonizing DNA aptamer, termed aptCTLA-4, using the cell-based SELEX and next-generation sequencing.
Results:
The aptCTLA-4 exhibits good binding affinity (dissociation constant, 11.8 nM). In vitro lymphocyte proliferation assays demonstrated that the aptCTLA-4 promotes T cell proliferation, and in vivo murine syngeneic tumor models further revealed its tumor-inhibitory effects.
Conclusion:
Our data suggest the translational potential of the aptCTLA-4 to be developed into a therapeutic aptamer.
