a drug for treating tumors

An anti-tumor drug and drug technology, applied in anti-tumor drugs, drug combinations, microorganisms, etc., can solve the problems of inability to prepare recombinant viruses, ineffective improvement of effects, and inability to successfully package, achieve optimal therapeutic effects, high cure rates, adaptable effect

Active Publication Date: 2022-06-03
JOINT BIOSCIENCES (SH) LTD
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  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

However, when using VSV in combination with PD-1 or PD-L1 antibodies for tumor immunotherapy, there are still at least the following problems: (1) Directly combining wild or attenuated VSV strains with PD-1 or PD-L1 antibodies, The cure rate is not high, and compared with using one therapy alone, the effect is not significantly improved; (2) Wild-type VSV still has certain safety risks, and it is currently known to have strong neurotoxicity to rodents, so it is considered for clinical use , it needs to be genetically modified to further reduce the risk of pathogenicity and improve the efficiency of treatment; (3) If genetic modification is carried out randomly, it may lead to poor oncolytic effect, or it may not be successfully packaged, and recombinant virus cannot be prepared at all

Method used

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  • a drug for treating tumors
  • a drug for treating tumors
  • a drug for treating tumors

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081]

[0083] (1) Construction of a plasmid. Take pVSV-XN2 plasmid as template, utilize PCR method to introduce different mutation as described in table 1

[0092] (6) After 48h, observe the fluorescence of cells in each well, and if there is fluorescence, record the well as being infected.

[0094] The results are shown in Figure 1. The replication expansion ability of JBS001 and JBS003 in lung cancer cells (LLC) in vitro is significantly high

[0100] (5) Add DMSO to each well, 100 μL / well, and place at 37°C for 10 minutes.

[0101] (6) Use a multifunctional microplate reader, shake for 2 minutes, and measure the OD value of each well at a wavelength of 570 nm.

[0102] The results are shown in Figures 2 and 3. The results showed that JBS001, JBS002, and JBS003 all exhibited good tumor cell killing.

[0103] 4. Different attenuated strains were tested for the difficulty of intracellular clearance. Tested with IFN-β indicator. Follow step 3 above

Embodiment 2

[0107]

[0108] The specific preparation methods of the JBS004~JBS007 are conventional techniques in the field, which are briefly described as follows. need to explain

[0109] (1) Attenuated strain plasmid construction. Artificially synthesized linking sequences with restriction enzyme sites Xho I and Mlu I, using

[0114] The tumor volume changes are shown in Figures 6-8. The results showed that each treatment group had a certain inhibition on the transplanted tumor.

[0115] The metastasis of cancer cells is shown in FIG. 9 . From Figures 6 to 9, it can be seen that the size of the transplanted tumor and the number of lung metastases

[0121] The results show: each treatment group has a certain therapeutic effect on melanoma, and the effect of the JBS004 group is particularly good.

[0123] C57BL / 6 mice of 6 to 8 weeks of age and weighing about 18 g were selected, and 2 × 10 mice were subcutaneously inoculated.

Embodiment 3

[0131] During the experiment, the body temperature and body weight of the mice were recorded every 2 days, and the results are shown in Figures 21-24. before administration and

[0132] Due to space limitations, the test results of all hematology and blood biochemical indicators are not listed here. Test result table

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Abstract

The invention belongs to the field of biotechnology, and in particular relates to an oncolytic virus vaccine and a drug for treating tumors in combination with immune checkpoint inhibitors. The invention provides a brand-new attenuated strain of oncolytic virus by performing site-directed mutation on the matrix protein M of vesicular stomatitis virus wild type virus. The attenuated strain can be used alone as a drug to treat tumors, and its safety and cure rate are superior to wild-type virus and other known attenuated strains. Based on the attenuated strain of oncolytic virus, the present invention also provides a vaccine applicable to tumor treatment by inserting NY-ESO-1 into the attenuated strain. The vaccine has a high cure rate and high biological safety. On the basis of the vaccine, the present invention also uses the vaccine in combination with immune checkpoint inhibitors to provide a drug that can efficiently treat multiple types of tumors; on the mouse lung cancer model, the cure rate can reach an astonishing 87.5% %, and has a better therapeutic effect on large tumors.

Description

a drug to treat cancer technical field [0001] The invention belongs to the field of biotechnology, in particular to a kind of medicine for the treatment of tumors. Background technique According to the national cancer statistics released by the National Cancer Center in January 2019, the incidence of malignant tumors in 2015 About 3.929 million people got sick and about 2.338 million died. On average, more than 10,000 people are diagnosed with cancer every day, and 7.5 people are diagnosed every minute Diagnosed with cancer. Solid tumors such as liver cancer, colorectal cancer, and female breast cancer are still the main malignant tumors in my country. malignant tumor (Cancer) has become one of the major public health problems that seriously threaten the health of the Chinese population. Although cancer treatment is currently available Great progress has been made in multidisciplinary comprehensive treatment such as surgery, chemotherapy, radiotherapy and molecul...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/395A61K35/766A61K39/00A61P35/00C12N15/47
CPCA61K35/766A61K39/3955A61K39/395A61K39/0011A61K39/001188A61P35/00C07K14/005C12N2760/20222A61K2039/505A61K2039/585A61K2039/876A61K2039/86A61K2300/00Y02A50/30C07K16/2818A61K39/39541A61K2039/545C12N2760/20243C12N2760/20232A61K45/06A61K2039/5254A61K2039/5256A61P17/00A61P11/00C12N2760/20234C12N2760/20262
Inventor 周国庆张译文张凡
Owner JOINT BIOSCIENCES (SH) LTD
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