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Method for preventing tumor-induced T cell aging and reversing immunosuppression capability of tumor-induced T cell, and use of tumor-induced T cell in antitumor immunological therapy

A tumor cell and inhibitory technology, which can be used in anti-tumor drugs, antibody medical ingredients, pharmaceutical formulations, etc., and can solve problems such as complex regulation of TLR signaling pathways

Active Publication Date: 2014-01-22
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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  • Method for preventing tumor-induced T cell aging and reversing immunosuppression capability of tumor-induced T cell, and use of tumor-induced T cell in antitumor immunological therapy
  • Method for preventing tumor-induced T cell aging and reversing immunosuppression capability of tumor-induced T cell, and use of tumor-induced T cell in antitumor immunological therapy
  • Method for preventing tumor-induced T cell aging and reversing immunosuppression capability of tumor-induced T cell, and use of tumor-induced T cell in antitumor immunological therapy

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Embodiment Construction

[0032] The experimental method is as follows:

[0033] 1. Human specimens and cell lines

[0034] Melanoma, breast, breast, and colon cancer specimens and paired normal tissues were obtained from Saint Louis University surgical inpatients. Normal human blood buffy coat (Buffy Coat) was obtained from the Bay Area Blood Center in Houston, USA. These studies have been approved by the School Research Review Board. Peripheral blood mononuclear cells (PBMC) were obtained by Ficoll-Paque separation. human naive CD4 + and CD8 + T cells were isolated using the 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 were cultured in keratinocyte culture medium (containing 25m...

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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] Activation of TOLL-like receptor 8 (TLR8) signaling as a novel and effective tumor immunotherapy drug and / or tumor vaccine adjuvant. Background technique [0002] Accumulating Evidence Shows Potent, 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 invasive and metastatic tumors. At present, many immunotherapy methods, such as cytokines, live tumor vaccines and adoptive immunotherapy, have shown certain effects in preclinical trials, but the overall clinical effect of these immunotherapies is not good [Rosenberg, S.A., Yang, J.C. & Rsetifo , N.P. Cancer immunotherapy: moving beyond current vaccine. Nat. Med 10, 909-15 (2004)]. Current studies have proved that the inhibitory microenvironment formed by tumors through various strategies is the main obstacle to m...

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Application Information

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