Oncolytic vaccinia virus with modified B5R gene for use in treating cancer

文档序号:53718 发布日期:2021-09-28 浏览:31次 中文

阅读说明:本技术 用于治疗癌症的具有修饰的b5r基因的溶瘤痘苗病毒 (Oncolytic vaccinia virus with modified B5R gene for use in treating cancer ) 是由 王尧河 袁明 于 2019-10-10 设计创作,主要内容包括:本发明涉及痘苗病毒载体,其包含编码插入到所述痘苗病毒的TK基因中的SCR1、SCR2、SCR3和SCR4结构域缺失的B5R基因(B5R SCR1~(-)SCR2~(-)SCR3~(-)SCR4~(-))的核酸序列。本发明还涉及包含痘苗病毒载体的组合物、使用该组合物的治疗方法、该组合物的医学用途和包含该痘苗病毒载体的试剂盒。本发明涉及核酸序列,该核酸序列编码痘苗病毒的SCR1、SCR2、SCR3和SCR4结构域缺失的B5R基因(B5R SCR1~(-)SCR2~(-)SCR3~(-)SCR4~(-))。(The present invention relates to vaccinia virus vectors comprising a B5R gene encoding a deletion of SCR1, SCR2, SCR3 and SCR4 domains inserted into the TK gene of the vaccinia virus (B5R SCR 1) ‑ SCR2 ‑ SCR3 ‑ SCR4 ‑ ) The nucleic acid sequence of (1). The invention also relates to compositions comprising vaccinia virus vectors, methods of treatment using the compositions, medical uses of the compositions, and kits comprising the vaccinia virus vectors. The present invention relates to nucleic acid sequences encoding deletions of the SCR1, SCR2, SCR3 and SCR4 domains of vaccinia virusB5R gene (B5R SCR 1) ‑ SCR2 ‑ SCR3 ‑ SCR4 ‑ )。)

1. A vaccinia virus vector comprising a B5R gene encoding deletion of SCR1, SCR2, SCR3 and SCR4 domains inserted into TK gene of the vaccinia virus (B5R SCR 1)-SCR2-SCR3-SCR4-) The nucleic acid sequence of (1).

2. The vaccinia virus vector of claim 1 wherein the native B5R gene remains intact.

3. The vaccinia virus vector of claim 1 further comprising a nucleic acid sequence encoding a biologically active protein inserted into the N1L gene of vaccinia virus.

4. The vaccinia virus vector of claim 3 wherein the biologically active protein is selected from the group consisting of a cytokine, an antibody fragment, a cytokine receptor, and a cytokine receptor fragment.

5. The vaccinia virus vector of claim 4 wherein the biologically active protein is a cytokine.

6. The vaccinia virus vector of claim 5 wherein the cytokine is selected from the group consisting of IL-21, GM-CSF, IL-2, IL-7, IL-12, IL-15, IL-18, and IFN- α or any combination thereof.

7. Vaccinia virus vector according to claim 1 and any of claims 3 to 5 wherein the B5R gene encoding SCR1, SCR2, SCR3 and SCR4 domain deletion (B5R SCR 1)-SCR2-SCR3-SCR4-) The nucleic acid sequence of (a) is as defined in figure 31.

8. The vaccinia virus vector of claim 4 wherein the biologically active protein is an immune checkpoint inhibitor molecule.

9. The vaccinia virus vector of claim 8, wherein the immune checkpoint inhibitor molecule is selected from the group consisting of soluble PD1, soluble PD-L1, soluble TIM-3, soluble CTLA-4, or any combination thereof.

10. Vaccinia virus vector according to any of claims 8 or 9 wherein the B5R gene encoding SCR1, SCR2, SCR3 and SCR4 domain deletion (B5R SCR 1)-SCR2-SCR3-SCR4-) The nucleic acid sequence of (a) is as defined in figure 31.

11. A composition comprising a vaccinia virus vector according to any of claims 1-7.

12. A composition comprising a vaccinia virus vector according to any of claims 8-10.

13. A method of treatment comprising administering the composition of claim 11 to a subject in need thereof to treat cancer.

14. A method of treatment comprising administering a composition according to claim 12 to a subject in need thereof to treat cancer.

15. A method of treatment comprising administering separately, sequentially or simultaneously a composition according to claim 12 and a composition according to claim 11.

16. The composition comprising a vaccinia virus vector according to claim 11 for use in treating cancer.

17. The composition comprising a vaccinia virus vector according to claim 12 for use in treating cancer.

18. The composition comprising a vaccinia virus vector according to claim 12 and the composition comprising a vaccinia virus vector according to claim 11 for separate, sequential or simultaneous use in cancer treatment.

19. A nucleic acid sequence encoding the B5R gene with deletions of the SCR1, SCR2, SCR3 and SCR4 domains of vaccinia virus (B5R SCR 1)-SCR2-SCR3-SCR4-)。

20. A kit comprising a vaccinia virus vector according to any of claims 1-6 and a pharmaceutically acceptable adjuvant, diluent, and/or buffer.

21. A kit comprising a vaccinia virus vector according to any of claims 8-9 and a pharmaceutically acceptable adjuvant, diluent, and/or buffer.

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