Method for activation of prodrug by tumor targeting bacteria and use thereof

A tumor-targeted and anti-tumor activity technology, applied in the field of using tumor-targeted bacteria to activate prodrugs, can solve the problems of intravenous injection of attenuated Salmonella without showing anti-tumor effect, insignificant curative effect, high cost, etc. The effect of bacterial anti-tumor efficiency and good therapeutic effect

Active Publication Date: 2013-02-27
NANJING UNIV
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Problems solved by technology

However, GDEPT therapy that relies on expression vectors has the following disadvantages: poor tumor targeting, insufficient transfection efficiency of tumor cells, poor stability in vivo, and high cost.
In 2002, Phase I clinical trials in the United States showed that a single dose of intravenous injection of attenuated Salmonella did not show a good anti-tumor effect (Toso JF et al., 2002, J Clin Oncol 20: 142-152.), so a single tumor bacterial treatment still has a curative effect However, there is an urgent need to develop a new strategy and system to enhance the efficacy of tumor bacterial therapy and reduce side effects

Method used

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  • Method for activation of prodrug by tumor targeting bacteria and use thereof
  • Method for activation of prodrug by tumor targeting bacteria and use thereof
  • Method for activation of prodrug by tumor targeting bacteria and use thereof

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Embodiment Construction

[0030] Taking attenuated Salmonella typhimurium with tumor targeting properties as a prodrug activation tool, 6-methylpurine-2-deoxyribonucleoside as a prodrug (6MePdR), and treating a mouse B16F10 melanoma model as an example:

[0031] 1. Analysis and detection of bacterial tumor targeting and prodrug activation activity:

[0032] (1) Establishment of B16F10 mouse melanoma subcutaneous model:

[0033] B16F10 cells were suspended in PBS to a concentration of 5×10 6 each / ml, and then each C57BL6 mouse was subcutaneously injected with 100 μL (5×10 5 cell), pay attention to the growth of the tumor, in about a week, the size of the tumor in situ grows to 30-50mm 3 , according to each mouse 10 5 Colony-forming unit (cfu) doses of attenuated Salmonella typhimurium VNP20009 were injected intraperitoneally.

[0034] (2) Tumor targeting analysis:

[0035]Spleen, liver and tumor were taken 5 days after administration, weighed, and homogenized according to the ratio of PBS:tissue=5:...

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Abstract

The invention belongs to the field of biotechnology and especially relates to a method for activation of a prodrug by tumor targeting bacteria and a use thereof. The method utilizes tumor targeting bacteria as natural prodrug activation tools; and the tumor targeting bacteria can realize constitutive expression of an endogenic prodrug activation enzyme gene thereby specifically activate a prodrug in tumor tissue and thus the activated prodrug can produce tumor-resistant effects. The method can be used for tumor treatment.

Description

1. Technical field: [0001] The invention belongs to the field of biological technology, and in particular relates to a method for activating prodrugs by using tumor-targeting bacteria and an application thereof. 2. Background technology: [0002] Targeted tumor therapy, which specifically kills tumor cells while avoiding damage to normal cells in the body, has always been an important direction and hotspot in tumor treatment research. Gene-Directed Enzyme Prodrug Therapy (GDEPT), as an important means of tumor-targeted therapy, has shown good therapeutic efficiency in various tumor animal models or clinically. The currently developed enzyme / prodrug therapeutic systems mainly include: herpes simplex virus thymidine kinase / guanosine (HSV-TK / GCV), cytosine deaminase / 5-fluorocytosine (CD / 5-FC) , Purine nucleotide phosphatase / 6-methylpurine-2-deoxyribonucleoside (PNP / 6MePdR) and the like. These enzymes that can be used to activate prodrugs are mainly derived from bacteria or vi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/74A61K48/00A61P35/00A61K47/46
CPCY02A50/30
Inventor 华子春陈果
Owner NANJING UNIV
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