A highly tropic bladder cancer-targeted tumor-killing adenovirus

A technology of adenovirus and bladder cancer, applied in the field of adenovirus for the treatment of bladder cancer, can solve the problems of lack of selective lysis of tumor cells, low replication ability of oncolytic adenovirus, difficulty in overcoming the immune system, etc., and achieve CAR receptor dependence Sexual problems, solving targeted problems, improving the effect of treatment

A technology of adenovirus and bladder cancer, applied in the field of adenovirus for the treatment of bladder cancer, can solve the problems of lack of selective lysis of tumor cells, low replication ability of oncolytic adenovirus, difficulty in overcoming the immune system, etc., and achieve CAR receptor dependence Sexual problems, solving targeted problems, improving the effect of treatment

CN104328140BInactive Publication Date: 2018-06-05LANZHOU UNIVERSITY
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  • A highly tropic bladder cancer-targeted tumor-killing adenovirus
  • A highly tropic bladder cancer-targeted tumor-killing adenovirus
  • A highly tropic bladder cancer-targeted tumor-killing adenovirus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0033] 1) Modification of the sequence of the ciliary region of adenovirus

[0034] Using the method of genetic engineering, the RGD sequence was integrated into the backbone plasmid of the adenovirus HI loop region to obtain pRGDAd. The fragment inserted into the RGD sequence was obtained by overlapping PCR (overlapping PCR) designed into the mutant sequence. Primers are as follows:

[0035] SEQ ID No 2 P1: 5’ CTGACTCTTAAGGACTAGTTTCGCGC 3’

[0036] SEQ ID No 3 P2: 5' GATCTCCACGAGTTGTGTCTCCTGT 3'

[0037] SEQ ID No 4 P3: 5'AACT CGTGGAGATCCAAGTGCATACTC 3'

[0038] SEQ ID No 5 P4: 5'ACGTAGGATCCATGCATGTTAATTAA 3' Using the pAdEasy-1 plasmid as a template and P1 and P2 as primers, bases 27241-30218 were cloned, and the 2979bp product upstream of the adenovirus HI loop was named RGD1.

[0039]

[0040] Using the pAdEasy-1 plasmid as a template, P3 and P4 as primers, clone 30219-33480, the 3283bp product downstream of the HI loop, named RGD2, and the PCR conditions were the s...

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Abstract

The present invention relates to high tropism bladder cancer targeting tumor-killing adenovirus, and discloses modified replication defective adenovirus for treating bladder cancer. According to the present invention, the RGD sequence is integrated into the adenovirus cilium zone to change the adenovirus tropism so as to improve the tropism on the bladder cancer lowly expressing the adenovirus receptor and solve the problem of low infection capability of the adenovirus vector on the bladder cancer lowly expressing the adenovirus receptor; in the tropism-modified adenovirus, the bladder epithelium-specific UPII promoter is adopted to control the expression of the suicide gene TK so as to construct the selectively expressing adenovirus; and the CAR receptor dependence problem of the adenovirus in the prior art and the targeting problem of the adenovirus in the prior art can be solved, and the treatment effect can be increased.

Description

technical field [0001] The present invention relates to a modified virus that can be used to treat tumors, specifically, the present invention relates to an adenovirus that can be used to treat bladder cancer. Background technique [0002] In my country, bladder cancer ranks first among urinary system tumors, causing serious losses in economic and social development, and the harm is very serious. Traditional radiotherapy and chemotherapy have disadvantages such as low anti-tumor ability, low killing index, and large side effects. The therapeutic effect is far from satisfactory. Therefore, it is very urgent to explore new treatment concepts, strategies and approaches to improve the therapeutic effect of bladder tumors. [0003] Adenovirus is an ideal carrier for tumor gene therapy and biotherapy. Adenoviral vector has become a commonly used gene therapy vector because of its advantages of easy preparation of high titer virus, ability to infect dividing and non-dividing cel...

Claims

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Application Information

Patent Timeline
05 Jun 2018
Publication
CN104328140B
IPC
C12N15/861; C12N15/66; A61P35/00
Inventors
王德贵; 田迎霞