- 专利标题: TUMOR-SPECIFIC ADENOVIRUS VECTORS AND THERAPEUTIC USES
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申请号: US15771110申请日: 2016-10-28
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公开(公告)号: US20190247452A1公开(公告)日: 2019-08-15
- 发明人: Michael Lan , Mary Breslin
- 申请人: Board of Supervisors of Louisiana State University and Agricultural and Mechanical College
- 国际申请: PCT/US16/59382 WO 20161028
- 主分类号: A61K35/761
- IPC分类号: A61K35/761 ; C12N15/86 ; A61P35/00 ; C12Q1/6886
摘要:
A conditionally replicating adenovirus were generated that can specifically replicate and express therapeutic genes in neuroendocrine tumors. The promoter-specific expression of the adenoviruses is regulated upstream by an INSM1 (insulinoma-associated-1) promoter that is silent in normal adult tissues but active in developing neuroendocrine cells and neuroendocrine tumors. By placing the INSM1-promoter with an insulator and two copies of neuronal restrictive silencer elements in an adenoviral vector, the construct can retain tumor specificity and drive expression of a mutated adenovirus E1A gene (424E1A) and the herpes simplex virus thymidine kinase gene. The INSM1-promoter-driven viruses could replicate specifically in the INSM1-positive cells and I NSM1-specific HSV-tk expression in combination with ganciclovir treatment displayed dose-dependent tumor cell-specific killing in insulinomas. When the INSM1-promoter driven HSV-tk was combined with 424E1A and INSM 1 p-HSV-tk viruses, the co-infected insulinoma expressed higher levels of HSV-tk and more efficient tumor suppression as compared to the INSM1 p-HSV-tk virus alone.
公开/授权文献
- US11246896B2 Tumor-specific adenovirus vectors and therapeutic uses 公开/授权日:2022-02-15
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