High tropism bladder cancer targeting tumor-killing adenovirus

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...

AI Technical Summary

Problems solved by technology

[0004] The following five obstacles in the prior art have affected the practical application of adenovirus vectors in the treatment of tumors: ① The CAR receptor (Coxsackie Adenovirus Receptor, CAR) dependence of adenovirus, and the entry of adenovirus into cells requires specificity on the cell surface The expression of the receptor CAR in tumor cells, especially in many malignant bladder tumors, the expression of CAR is missing, resulting in low transfection efficiency of adenovirus in tumor cells and poor oncolytic effect

② The targeting of adenovirus, because the adenovirus itself lacks the ability to selectively lyse tumor cells, the side effects are relatively large

③Oncolytic adenovirus has low replication ability, and the oncolytic effect of lysing tumors by replication is poor

④Security issues

⑤ Difficulty in administering the drug, the virus will be cleared by the body’s immune system after intravenous injection, and it is difficult to reach the effective amount of virus in the local tumor

However, it is difficult to overcome the immune system's ability to clear the virus, and it is difficult to achieve a sufficient therapeutic concentration, which makes it difficult to treat a considerable number of solid tumors.

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