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Use of glucosylceramide synthase gene-deficient t cell and therapeutic utilization thereof

A technology of ceramide and glucose, which is applied in the field of T cells with reduced or lost function, and can solve the problem of unclear correlation between cancer immunity and glycosphingolipids

Pending Publication Date: 2021-06-04
SCHOOL CORP AZABU VETERINARY MEDICINE EDUCATIONAL INSTITUTION +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, at present, there are still many unknowns about the relationship between T cell-involved cancer immunity and glycosphingolipids

Method used

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  • Use of glucosylceramide synthase gene-deficient t cell and therapeutic utilization thereof
  • Use of glucosylceramide synthase gene-deficient t cell and therapeutic utilization thereof
  • Use of glucosylceramide synthase gene-deficient t cell and therapeutic utilization thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0087] 1. Analytical analysis of T cell specific UGCG gene lack mice

[0088] To the T cell specific UGCG gene lack of mice, Melanoma, the growth of tumors and the survival time of mice. In the experiment of the mice performed in the present embodiment, all mice were all raised in SPF (Specific Pathogen Free, there was no specific pathogen) environment, approved by the Metal Experimental Committee, in accordance with guidelines.

[0089] T cell-specific UGCG gene lack mice were made by mirings of the UGCG gene lacking Flox mice (Yamashita et al, Genesis 43: 175-180 2005) with T cell specific CRE mice. In addition, mice without CRE genes in fetillas were used as a control.

[0090] Mouse melanoma cells (B16F110: obtained from Northeast University Medical Cell Resources Center Cell Bank) 1 × 10 5A 100 μl of Dalbu modified Igel (DMEM) medium containing 30% Matrigel (Corning) was injected into the back subcutaneous mice with T cell specific UGCG gene lack mice with control mice. After...

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Abstract

The present invention provides: an activated T cell in which the expression of an immune checkpoint molecule is suppressed; a method for preparing the T cell; and a method for screening a substance which is usable in preparing the T cell. More specifically, a means for solving the problem of the present invention comprises: a method for producing or inducing a T cell in which the expression of an immune checkpoint molecule is not induced, said method comprising reducing or losing the function of glucosylceramide synthase (UGCG) or a ganglioside of a T cell; and a T cell having been produced or induced by this method.

Description

Technical field [0001] The present invention relates to the use of a functionally reduced or loss of glucose neuroyamide synthase. Background technique [0002] At present, as a treatment of cancer, an anticancer agent is used, and an immunotherapy such as an anti-cancer agent is carried out in addition to surgery. Among them, the treatment of immunougal point inhibitors is to inhibit the immunosuppressive signal transfer by hindering the binding of the immunogenic examination point molecules and their ligands, the treatment of activation inhibition of T cells is one of the concerns of treatment in recent years. [0003] So far, various immunoconition-based molecules have been set up as their representative molecules, and CTLA-4 (Cytotoxic T-Lymphocyte Associated Antigen-4 (cytotoxic T lymphocyte-related antigen-4), PD-1 ( Programmed Cell Death-1 (Programmable Death Receptor-1) / CD279), etc. The activation of T cells is induced by the combination of B7 (CD80 / CD86) on the antig...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/54C12N5/0783C12N5/10C12Q1/48G01N33/15G01N33/50C12N9/10A61K35/17A61K45/00A61P35/00A61P43/00
CPCA61K35/17A61P43/00A61P35/00C12Q1/48C12N9/1048C12N5/0636C12N2501/515C12N2501/51C12N2501/2302G01N33/57484G01N33/5038G01N33/505A61K31/5375G01N33/5005C12Y204/0108C12N9/1051
Inventor 山下匡永根大干池田辉雄宫武昌一郎冈本真理子
Owner SCHOOL CORP AZABU VETERINARY MEDICINE EDUCATIONAL INSTITUTION