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A method for preparing a drug for preventing tumor cells from inducing T cell aging and reversing its immunosuppressive ability and its use in anti-tumor immunotherapy

A tumor cell and immunosuppressive technology, applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the complex regulation of TLR signaling pathways and other issues

Active Publication Date: 2016-01-20
彭光勇
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Problems solved by technology

These contradictory results further illustrate that the regulation of TLR signaling pathways in tumor and immune cells is complex and varies between different tumors and different TLR ligands

Method used

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  • A method for preparing a drug for preventing tumor cells from inducing T cell aging and reversing its immunosuppressive ability and its use in anti-tumor immunotherapy
  • A method for preparing a drug for preventing tumor cells from inducing T cell aging and reversing its immunosuppressive ability and its use in anti-tumor immunotherapy
  • A method for preparing a drug for preventing tumor cells from inducing T cell aging and reversing its immunosuppressive ability and its use in anti-tumor immunotherapy

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Embodiment Construction

[0032] The experimental method is as follows:

[0033] 1. Human specimens and cell lines

[0034] The specimens of melanoma, breast cancer, breast cancer, colon cancer and matched normal tissues were obtained from hospitalized patients of Saint Louis University. The white blood cell layer of normal humans (BuffyCoat) comes from the Blood Center in the Gulf of Houston, USA. These studies have been approved by the school’s research review committee. Ficoll-Paque isolated peripheral blood mononuclear cells (PBMC). Human childish CD4 + And CD8 + T cells were isolated and obtained using EasySep Enrichment Kit (StemCell Technologies). Different types of tumor cell lines (melanoma, breast cancer, ovarian cancer, prostate cancer, colon cancer and squamous cell carcinoma) and normal breast tissue-derived cells (BN) were purchased from the American Tissue Bank (ATCC) or established in our laboratory. Breast cancer (BC) and colon cancer (CC) cell lines are cultured in keratinocyte culture...

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Abstract

The invention provides a method for preventing tumor-induced T cell aging and reversing immunosuppression capability of the tumor-induced T cell. A ligand of a TOLL like receptor 8 is provided to a cell; a TOLL like receptor 8 (TLR8) signal channel in a tumor cell is activated; the tumor-induced T cell aging is blocked up, so as to improve the antitumor immunity. The ligand of the TOLL like receptor 8 is characterized by being oligonucleotides and comprising adenine, guanine, a main chain connecting bond for connecting the guanine and nuclease resistance residue of adjacent nucleic acid bases (preferably a chemical bond is phosphorothioate); a nucleic acid synthesis sequence is 5'-AGG...GA-3'; G represents guanine; A represents adenine; G and G are modified by a dithio phosphate ester bond; the number of G may be 3 to10 in difference; an acid synthesis sequence of a common ligand Poly-G3 is 5'-AGGGA-3'. By injecting TLR8 ligand Poly-G3 into the tumor, the inhibitory effect of a CD8<+>T cell can be significantly enhanced.

Description

Technical field [0001] Activate TOLL-like receptor 8 (TLR8) signal as a new and effective tumor immunotherapy drug and / or tumor vaccine adjuvant. Background technique [0002] More and more evidence shows effective and functional CD4 + And CD8 + T cells play a key role in tumor immune surveillance and anti-tumor immunity. Therefore, how to regulate immune cells to efficiently recognize and eliminate tumor cells has become a new strategy for the treatment of aggressive and metastatic tumors. At present, many immunotherapy methods, such as cytokines, live tumor vaccines and adoptive immunotherapy, have shown certain effects in pre-clinical trials, but the overall clinical effects of these immunotherapies are not good [Rosenberg,SA,Yang,JC&Rsetifo, NPCancerimmunotherapy:movingbeyondcurrentvaccine.Nat.Med10,909-15(2004)]. Current studies have proved that the inhibitory microenvironment formed by tumors through various strategies is the main obstacle to mobilizing the body's immune ...

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/39A61K31/7088A61P35/00
Inventor 彭光勇叶健
Owner 彭光勇
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