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논문 기본 정보

자료유형
학술저널
저자정보
Da-Hyun Kim (Yonsei University College of Medicine) Seul Lee (Yonsei University) Hyeok Gu Kang (Yonsei University College of Medicine) 박현우 (연세대학교) 이한웅 (연세대학교) Dongin Kim (ABL Bio Inc.) Dong-Hoon Yoem (ABL Bio Inc.) Jin-Hyung Ahn (ABL Bio Inc.) Eunsin Ha (ABL Bio Inc.) Weon-Kyoo You (ABL Bio Inc.) Sang Hoon Lee (ABL Bio Inc.) 김석준 (조선대학교) 전경희 (연세대학교)
저널정보
대한생화학·분자생물학회 BMB Reports BMB Reports 제53권 제10호
발행연도
2020.1
수록면
533 - 538 (6page)

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Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 therapeutic antibody (anti-hDLL4) or ABL001 slightly reduced GC cell growth in monolayer culture; however, they significantly inhibited cell growth in 3D-culture, suggesting a reduction in the cancer stem cell population. Treatment with anti-hDLL4 or ABL001 also decreased GC cell migration and invasion. Moreover, the combined treatment of irinotecan with anti-hDLL4 or ABL001 showed synergistic antitumor activity. Both combination treatments further reduced cell growth in 3D-culture as well as cell invasion. Interestingly, the combination treatment of ABL001 with irinotecan synergistically reduced the GC burden in both xenograft and orthotopic mouse models. Collectively, DLL4 inhibition significantly decreased cell motility and stem-like phenotype and the combination treatment of DLL4/VEGF bispecific therapeutic antibody with irinotecan synergistically reduced the GC burden in mouse models. Our data suggest that ABL001 potentially represents a potent agent in GC therapy. Further biochemical and pre-clinical studies are needed for its application in the clinic.

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