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Tumor immunotherapy target aiming at tumor-associated macrophages

A technology related to tumor cells and tumors, which is applied in gene therapy, antineoplastic drugs, microbial measurement/testing, etc., and can solve problems such as difficult to come up with treatment plans

Active Publication Date: 2018-05-11
INST OF RADIATION MEDICINE ACAD OF MILITARY MEDICAL SCI OF THE PLA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the high heterogeneity of tumor cells, it is difficult to propose effective treatment options from the perspective of genetic diversity and epigenetics

Method used

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  • Tumor immunotherapy target aiming at tumor-associated macrophages
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  • Tumor immunotherapy target aiming at tumor-associated macrophages

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0099] Example 1, LSECtin promotes tumor formation

[0100] 1. LSECtin promotes tumorigenesis and tumor progression in mice with spontaneous breast cancer

[0101] 1. Detection of tumor volume in spontaneous breast cancer model mice

[0102] Spontaneous breast cancer model mouse LSECtin + / + PyMT and LSECtin in spontaneous breast cancer model mice - / - PyMT was bred and bred at the Experimental Animal Platform of the Academy of Military Medical Sciences. Tumor volumes were measured starting at 13 weeks. After that, observe once a week, use a vernier caliper to measure the long diameter a and short diameter b of the mouse tumor respectively, and calculate the tumor volume. The formula for calculating the tumor volume is 0.5*ab 2 . Up to 22 weeks, mice were sacrificed.

[0103] The detection results of tumor volume in spontaneous breast cancer model mice are as follows: figure 1 (a), at 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 weeks, LSECtin + / + - The tumor volumes o...

Embodiment 2

[0116] Example 2, Detection of LSECtin expression level in tumor microenvironment

[0117] 1. Detection of the expression level of LSECtin in the microenvironment of mouse breast cancer

[0118] 1. MMTV-PyMT spontaneous breast cancer mouse model, human-nude mouse breast cancer transplantation model and isolation of tumor-infiltrating myeloid cells from clinical samples

[0119] (1) Preparation of digestive solution: 20 ml of 1640 medium (Hyclone Company, SH30809), 20 mg of collagenase IV and 1 mg of DNase I were mixed to obtain a digestive solution, which was filtered through a 0.45 μm filter membrane.

[0120] (2) The mammary tumor tissue or fresh clinical tumor samples were stripped from the MMTV-PyMT spontaneous breast cancer mice and the human-nude mouse breast cancer transplantation model mice for 8 weeks, shredded, and put into the step ( 1) In the prepared digestive solution, the tumor digestive solution was obtained, and digested at 37° C. for 40 minutes.

[0121] (3...

Embodiment 3

[0170] Example 3. Tumor cells in various clinical samples express BTN3A2 and BTN3A3

[0171] 1. Isolation of tumor cells from clinical samples

[0172] (1) Preparation of digestive solution: 20 ml of 1640 medium (Hyclone Company, SH30809), 20 mg of collagenase IV and 1 mg of DNase I were mixed to obtain a digestive solution, which was filtered through a 0.45 μm filter membrane.

[0173] (2) Take fresh tumor tissues from clinical patients, cut them into pieces, put them into the digestive solution prepared in step (1) to obtain tumor digestive solution, and digest them at 37° C. for 40 minutes.

[0174] (3) Filter the tumor digestion solution with a 70 μm filter, and centrifuge at 250 g for 10 min.

[0175] (4) Wash the tumor cells in the tumor digestion solution with 1640 medium for 3 times, and obtain enriched tumor cell subpopulations by flow cytometry: the specific steps are as follows: the living cell population is passed through SSC-H / FSC-W and SSC-W / FSC-H removes adher...

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Abstract

The present invention discloses a tumor immunotherapy target aiming at tumor-associated macrophages. Experiments prove that LSECtin, BTN3A2 and BNT3A3 can promote tumor progression by promoting of thestemness maintenance of tumor cells, more specifically, formation of tumor cell spheres, expression of stem transcription factors and tumor progression in a mice tumor model are promoted; by inhibition of interaction of the LSECtin with the BTN3A2 and the BTN3A3, the tumor progression can be effectively slowed down, more specifically, the incidence of tumors is reduced, and tumor volume growth can be slowed down.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a tumor immunotherapy target for tumor-associated macrophages. Background technique [0002] The global incidence of cancer has been on the rise since the late 1970s. At present, the treatment methods for tumors mainly include surgery, radiotherapy, chemotherapy, endocrine therapy, biological targeted therapy and adjuvant therapy of traditional Chinese medicine, etc. The fundamental problem that plagues cancer treatment is drug resistance and recurrence after cure. Studies have shown that the root cause of drug resistance and recurrence lies in the enhancement of tumor cell stemness. For example, triple-negative breast cancers characterized by estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 2 (HER2) negative tend to be considered to have a higher tumor stemness property. There are also research results showing that most non-triple-ne...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K45/00A61K39/395A61K31/7088A61K48/00A61P35/00A61P35/04C12Q1/68C12Q1/02
CPCA61K38/1732A61K39/395A61K45/00A61K48/0058G01N33/5091A61K31/7088C12Q1/6886C12Q2600/158
Inventor 唐丽贺福初柳迪王兴
Owner INST OF RADIATION MEDICINE ACAD OF MILITARY MEDICAL SCI OF THE PLA
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