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Artificial recombination selection replication type adenovirus and application

An adenovirus, replication-type technology, applied in applications, antiviral agents, viruses/phages, etc., can solve problems such as unsatisfactory curative effect, and achieve the effect of avoiding serious toxic and side effects

Inactive Publication Date: 2007-08-15
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Biological therapy has unique advantages. It can distinguish normal cells from tumor cells through various ways, and can produce specific killing effect on tumor cells, that is, the targeting of treatment, the treatment plan can be individualized, and the damage to the body is small. The effect in the experiment is remarkable, and some treatment methods have become important adjuvant tumor treatment methods in clinical application, but the overall effect is still not satisfactory

Method used

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  • Artificial recombination selection replication type adenovirus and application
  • Artificial recombination selection replication type adenovirus and application
  • Artificial recombination selection replication type adenovirus and application

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0018] Example 1: Killing effect of rsAd-MK-TNFa (ZUCI008) on RKO cells (colon cancer cell line)

[0019] Select 5 virus concentrations: MOI=0.02, 0.2, 2, 20, 200 and blank control, add them to RKO cells in the exponential growth phase, and use the MTT method to observe its effect on the growth of RKO cells. We observed that The inhibitory effect of the virus on tumor cells has a time effect, and its inhibitory effect on tumor cells is enhanced with the prolongation of the action time (see Figure 1-1). The growth of tumor cells was significantly inhibited after 5 days of administration, and the inhibitory effect on tumor cells was concentration-dependent, and the inhibitory effect on cells was enhanced as the concentration increased (see Figure 1-2).

example 2

[0020] Example 2: The killing effect of rsAd-MK-TNFa on smmc7721 cells (hepatoma cell line)

[0021] Five virus concentrations were selected: MOI=0.02, 0.2, 2, 20, 200 and blank control, and added to smmc7721 cells in the exponential growth phase, and the MTT method was used to observe its effect on the growth of RKO cells. We observed The inhibitory effect of the virus on tumor cells has a time effect, and its inhibitory effect on tumor cells is enhanced with the prolongation of the action time (see Figure 2-1). After 5 days of administration, the growth of tumor cells was significantly inhibited, and the inhibitory effect on tumor cells was concentration-dependent, and the inhibitory effect on cells was enhanced with the increase of concentration (see Figure 2-2).

example 3

[0022] Example 3: Observation of the inhibition rate of rsAd-MK-TNFa on different tumor cells

[0023] From the experiments in Example 1 and Example 2, we can see that the inhibitory effect of rsAd-MK-TNFa on tumor cells is weak at MOI=0.02, 0.2, 2, so we choose MOI=10, 100, 1000 three concentration gradients, using the MTT method to observe the inhibitory effect of rsAd-MK-TNFa on tumor cells, because in the previous growth curve experiment we found that the effect of rsAd-MK-TNFa on tumor cells began to appear after the third day , so we observed the results of rsAd-MK-TNFa on day 3 and day 5 respectively, see Figure 3-1 and Figure 3-2. We observed that rsAd-MK-TNFa has a certain inhibitory effect on tumor cells, and the inhibitory effect on different tumor cells is very different. In the solid tumor cell lines tested, the inhibitory effect on sw480 is the largest, followed by Bcap37 , while it has the greatest inhibitory effect on HL60 in leukemia cell lines, and it also h...

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Abstract

The invention discloses an artificial reconstructing selection replicative form adenovirus, which is characterized by the following: possessing nucleic acid sequence of SEQ ID NO.1; duplicating in virus selective infection tumour cell; carrying TNFalpha gene of Midkine starting; generating TNFalpha in Midkine high expression tumor cell; causing extinction of tumor cell; generating lethalling action for tumor cell with duplication of virus, expressing TNFalpha and antiviral cell immunity. This invention does not express Midkine, which can be used to preparing medicine for treat specificity lethal adenovirus and provide new method to treat tumor.

Description

technical field [0001] The invention belongs to biological technology, and relates to the artificial recombinant tumor-specific killing adenovirus (rsAd-MK-TNFa), which can be used in the preparation of treatment-specific killing adenovirus drugs. Background technique [0002] In recent years, the population is aging, environmental pollution is increasing, and unhealthy lifestyles such as smoking are increasing day by day. The incidence of malignant tumors is also increasing year by year, but the treatment effect on malignant tumors is rarely improved. Therefore, how to effectively improve the cure rate of malignant tumors is an important problem to be solved in current tumor research. Conventional treatment methods are surgery, chemotherapy, and radiotherapy. Although surgery can remove tumor cells in resectable sites, it can't do anything for the treatment of distant metastasis. However, radiotherapy and chemotherapy have great damage to the body, and the specificity of k...

Claims

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Application Information

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IPC IPC(8): C12N7/01C12N15/861C12N15/28A61K48/00A61P31/12
Inventor 陆巍郑树
Owner ZHEJIANG UNIV
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