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Application of cGAMP and derivatives thereof to preparation of anti-tumor vaccines

A derivative and anti-tumor technology, applied in the field of preparation of anti-tumor vaccines, can solve problems such as inability to effectively induce anti-tumor immune responses, low immunogenicity, and lack of immune cofactors

Inactive Publication Date: 2017-03-29
LIAOCHENG CITY ORIENT BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the expression of TSA in tumor cells is low, and the expression of some immune cofactors is lacking, and the immunogenicity is low, so it is often unable to effectively induce anti-tumor immune response

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Example 1: Preparation of GS-CSF tumor cell vaccine

[0016] The mouse cell colony factor GM-CSF gene (gene ID: 12981) was synthesized from Nanjing GenScript Biotechnology Co., Ltd. pLenti and packaged viral vectors were purchased from Life Technology. Colorectal cancer cells MC38, melanoma cells B16, prostate cancer TRAMP-C2 cells, Hepa 1-6 liver cancer cells, Lewis lung cancer cells, and MDA-MB-231 breast cancer cells were purchased from ATCC in the United States. The GM-CSF gene was cloned into the pLenti vector, and co-transfected with the packaging plasmid into 293e cells, and the supernatant containing the packaging virus was collected. For the method of preparing GM-CSF lentivirus, refer to the Life Technology lentivirus preparation manual. The prepared lentiviruses were used to infect colorectal cancer cells MC38, melanoma cells B16, prostate cancer TRAMP-C2 cells, Hepa 1-6 liver cancer cells, Lewis lung cancer cells, MDA-MB-231 breast cancer cells, and add res...

Embodiment 2

[0017] Embodiment 2: cGAMP preparation

[0018] cGAMP (cyclization-GMP-AMP) synthetase cGAS and cGAMP are catalyzed and synthesized by cyclization cGMP-AMP dinucleotide synthase (cGAS) under activation conditions after binding to DNA according to literature method. The purity is above 98%. (Ping wei Li, et al., Immunity, 2013, 39(6), 1019-1031.) Adenosine (guanosine) 5'-α thio(selenium) phosphorotriphosphate was synthesized according to literature method (Caton-Williams Julianne et al., Science China, Chemistry, 2012, 55(1), 80-89; Boyle Nicholas A., Nucleosides, Nucleotides and Nucleic Acids, 2005, 24, 1651-1664.). According to the method for preparing cGAMP, the prepared recombinant cGAS enzyme is used to catalyze the preparation of sulfur (seleno)phosphoryl cyclic dinucleotide cGAMP.

Embodiment 3

[0019] Example Three: Establishment of Mouse Tumor Model and Vaccine Injection

[0020] 1. Establishment of tumor-bearing mouse model

[0021] C57BL / 6 female mice, 6-8 weeks old, were purchased from Shanghai Slack Experimental Animal Co., Ltd. The tumor cells used in tumor model mice are tumor cells that do not express GM-CSF, including: colorectal cancer cell MC38, melanoma cell B16, prostate cancer cell TRAMP-C2, liver cancer cell Hepa 1-6, lung cancer cell Lewis, breast cancer cell Cell MDA-MB-231. Cell culture and passage were carried out according to the corresponding cell culture methods, and were used in the establishment of tumor mouse models in the logarithmic phase. Collect the cells in the logarithmic phase of the mouse tumor cells, make a cell suspension with a concentration of (1-5×10e6) / ml per milliliter, inject 0.2 ml of the cell suspension into the axilla of the right forelimb of the mouse (the number of cells is 2-10 ×10e5 per mouse), the tumor grew to a di...

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Abstract

The invention belongs to the fields of biomedical technologies and tumor immunotherapy, and particularly relates to application of cyclic dinucleotides (cGAMP) and derivatives thereof to preparation of anti-tumor vaccines. Researches prove that the cGAMP, as vaccine adjuvant, can strengthen the effect of tumor vaccines, retrain growth of various tumor cells, have the remarkable anti-tumor effect and be used for preparation of the anti-tumor vaccines. A model of mouse transplantable subcutaneously tumors proves that as the vaccine adjuvant, the cGAMP has remarkable restraint effect to mouse transplantable subcutaneously tumors of colorectal cancer cells MC38, melanoma cells B16, prostate cancer cells TRAMP-C2, hepatoma carcinoma cells Hepa 1-6, lung carcinoma cells Lewis and breast cancer cells MDA-MB-231, and therefore the cGAMP can be used for preparation of the anti-tumor vaccine adjuvant as well as tumor treatment.

Description

technical field [0001] The invention belongs to the fields of biomedical technology and tumor immunotherapy, and specifically relates to the application of cyclic dinucleotide (cGAMP) and its derivatives in anti-tumor and preparation of anti-tumor vaccines. Background technique [0002] Tumor is one of the major diseases that seriously endanger human life and health. It is characterized by excessive cell proliferation and abnormal differentiation. WHO experts predict that in 2020, the incidence of tumors in the global population will reach 20 million, and the death toll will reach 12 million. Tumors will become the number one killer of humans in this century and pose the most serious threat to human survival. The morbidity and mortality of lung cancer, colorectal cancer, gastric cancer, and liver cancer rank among the forefront of various malignant tumors. According to the statistics released by the National Cancer Registry Center (2012 China Cancer Registry Annual Report),...

Claims

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Application Information

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IPC IPC(8): A61K39/39A61K39/00A61P35/00A61P37/04
Inventor 张跃茹袁红谭瀛轩向道凤
Owner LIAOCHENG CITY ORIENT BIOMEDICAL TECH CO LTD