Abstract 1946: SJP1604, a novel nucleolin-targeted anti-cancer drug for acute myeloid leukemia using aptamer-drug conjugation technology
| العنوان: | Abstract 1946: SJP1604, a novel nucleolin-targeted anti-cancer drug for acute myeloid leukemia using aptamer-drug conjugation technology |
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| المؤلفون: | Jihyun Um, Hee Jong Shin, Sung Hwan Moon, Eui Hwan Jo, Su Jin Lee, Dohyeong Lee, Min-Hyo Ki, Yongbin Park |
| المصدر: | Cancer Research. 78:1946-1946 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Cancer Research, business.industry, medicine.medical_treatment, Azacitidine, Myeloid leukemia, Decitabine, Cancer, medicine.disease, Targeted therapy, Oncology, hemic and lymphatic diseases, Cancer cell, Cytarabine, medicine, Cancer research, business, Nucleolin, medicine.drug |
| الوصف: | Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are cancers characterized by the rapid growth of abnormal white blood cells. Generally, cytarabine (Ara-C), azacitidine, and decitabine are treated as the standard first-line chemotherapy for AML/MDS. Although the therapy leads to high rates of remission, approximately 30% of the treated patients are refractory and more than 50% of them face a relapse because of the occurrence of drug resistance and high toxicity. Therefore, there is a strong unmet need for the next-generation targeted therapy to overcome drug resistance and reduce toxicity in AML/MDS. Aptamers mostly consist of oligonucleotides, which can specifically bind to their target molecules with high affinity. Here, we designed a synthetic DNA aptamer-nucleoside drug conjugate (SJP1604) specific for nucleolin, which is highly expressed only on the cell membrane of cancer cells. In particular, AML and ALL (acute lymphoblastic leukemia) cells are known to express the highest mRNA level of nucleolin among various cancer cells, relatively. Owing to the unique conformational property of SJP1604, it can be delivered into cancer cells with its high targeting ability and plasma stability. In this study, we verified that SJP1604 selectively targeted cancer cells by nucleolin-binding on the cancer cell membrane in the drug uptake assay. SJP1604 also exhibited a long-lasting plasma stability in 50% human plasma up to 48 hours in sharp contrast to unstability of general aptamers. Furthermore, SJP1604 inhibited not only the growth of human AML/MDS cell lines (MV-4-11, HL-60, MOLM-13, THP-1 and KG-1) but also drug-resistant cell lines (cytarabine-, azacitidine- and decitabine-resistant MOLM-13, cytarabine-resistant HL60 and cytarabine-resistant MV-4-11). Interestingly, SJP1604 showed the significantly reduced IC50 values with the decreased expression level of nucleolin in cytarabine-, azacitidine- and decitabine-resistant MOLM-13 while cytarabine caused no effect on the cell growth and the expression of nucleolin of the same resistant cell lines. Intravenous administration of SJP1604 (150 mg/kg) led to tumor regression and improved survival rate in MOLM-13 xenograft mouse model. In conclusion, these findings suggest that SJP1604 could be developed as a first-in-class drug for novel targeted therapy of AML/MDS with less drug toxicity as well as an orphan drug for overcoming drug resistance of AML/MDS, using aptamer-drug conjugation technology. Citation Format: Jihyun Um, Dohyeong Lee, Yongbin Park, Sung Hwan Moon, Su Jin Lee, Min-Hyo Ki, Hee Jong Shin, Eui Hwan Jo. SJP1604, a novel nucleolin-targeted anti-cancer drug for acute myeloid leukemia using aptamer-drug conjugation technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1946. |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::ef3eb3760434394840e999c7871b2119 https://doi.org/10.1158/1538-7445.am2018-1946 |
| رقم الأكسشن: | edsair.doi...........ef3eb3760434394840e999c7871b2119 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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