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Reagent for enhancing capacity of homing CAR-T cell to solid tumor tissue

A cell and reagent technology, applied in the field of biomedicine, can solve the problems of DPP4 biological function and its mechanism of action are not very clear, to achieve the effect of enhancing tumor enrichment ability, enhancing curative effect, and improving therapeutic effect

Pending Publication Date: 2019-04-09
CHONGQING PRECISION BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the biological function and mechanism of DPP4 in different tumors are still not very clear.

Method used

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  • Reagent for enhancing capacity of homing CAR-T cell to solid tumor tissue
  • Reagent for enhancing capacity of homing CAR-T cell to solid tumor tissue
  • Reagent for enhancing capacity of homing CAR-T cell to solid tumor tissue

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 A reagent that enhances the ability of CAR-T cells to homing to solid tumor tissues

[0049] A reagent for enhancing the ability of CAR-T cells to homing to solid tumor tissue, the DPP4 inhibitor is sitagliptin.

Embodiment 2

[0050] Example 2 A CAR-T cell and its preparation

[0051] (1) Isolation of PBMC (peripheral blood mononuclear cells)

[0052] 20% volume of hydroxyethyl starch (Shandong Qidu Pharmaceutical Co., Ltd.) was added to the peripheral blood of healthy donors, mixed well, and then allowed to stand at room temperature for 30 minutes. PBMCs were isolated using human lymphocyte separation medium (Tianjin Haoyang Biological Products Co., Ltd.). The isolated cells were resuspended with fresh 1640 culture medium (Gibco Company) containing 10% FBS, and placed in a CO2 incubator at 37° C. for 2 hours to remove mononuclear cells.

[0053] (2) Activation, virus infection and expansion of T cells

[0054] CD3 (Miltenyi Biotec) and CD28 (Miltenyi Biotec) coated PBMCs obtained in activation (1). The activated cells were added to the activated T cells infected with CAR virus, and the CAR-T cells infected with the virus were expanded and cultivated with 1640 (Gibco company) culture medium conta...

Embodiment 3

[0058] Example 3 DPP4 Inhibitor Enhances the Ability of CAR-T Cells to Chemotaxis to Tumor Cells

[0059] Since in vitro chemotaxis experiments are difficult to perform without the presence of chemokines, CXCL10 (PeproTech) was added exogenously to the in vitro experiments to enhance the sensitivity of in vitro experiments, but it did not affect the overall experimental trend.

[0060] After digesting and collecting the LoVo (colorectal cancer cell line) and Hela (cervical cancer cell line) cells in good growth state, they were plated on a 6-well plate at 37°C with a constant temperature of CO 2 Culture in the incubator for 2 days. In the experimental group, 0.5 mg / mL DPP4 inhibitor sitagliptin was added before the cells were collected, and reacted for 30 min. Collect the cell supernatant, centrifuge to remove cell debris, take 600uL cell supernatant into a 24-well plate, add 100μg / mL CXCL10 factor, and put it into a transwell chamber with a pore size of 5μm. Collect and cou...

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Abstract

The invention belongs to the technical field of the biological medicine, and specifically relates to a CAR-T cell, a reagent for enhancing capacity of homing CAR-T cell to solid tumor tissue, and application thereof. The reagent is a DPP4 inhibitor, includes but not limited to sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin. The CAR-T cell expression includes ScFv, a hinge structure and a transmembrane structure, and a chimeric antigen receptor (CAR) of an intracellular activation signal domain; an amino acid sequence of the hinge structure is as shown in SEQ ID NO.1 or SEQID NO.2 or SEQ ID NO.3 or SEQ ID NO.4 or SEQ ID NO.5. The invention provides a new application of the DPP4 inhibitor for participating tumor treatment. The reagent can enhance the tumor homing capacity and tumor enrichment capacity of the CAR-T cell, and a therapeutic effect on the solid tumor by the CAR-T therapy is improved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a CAR-T cell, a reagent for enhancing the ability of the CAR-T cell to homing to solid tumor tissue, and an application thereof. Background technique [0002] The full name of CAR-T is chimeric antigen receptor T cell immunotherapy, which has achieved good results in hematological tumors, but the effect of CAR-T in solid tumors is not as good as that of hematological tumors. One of the main reasons is that CAR -T is difficult to enter into solid tumors, and solid tumors are highly heterogeneous, and solid tumor targets are often expressed in normal tissues. If CAR-T cells cannot "precisely" target tumor tissues, there will be safety issues such as off-target risks , These all affect the efficacy of CAR-T cells in the treatment of solid tumors. therefore, It is necessary to improve the tumor homing and infiltration capabilities of CAR-T cells. [0003] DPP4, also...

Claims

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Application Information

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IPC IPC(8): C12N5/10A61K35/17A61P35/00
CPCA61P35/00C12N5/0636C07K14/7051C07K16/3007C07K16/3069C07K2319/03C07K2319/02C12N2510/00A61K45/06A61K39/0011A61K31/4985A61K2039/5156C07K2319/33C07K2319/74A61K2300/00
Inventor 张巍陈运帆赵永春徐艳敏赵文旭黄霞单娟娟陈军张茜真
Owner CHONGQING PRECISION BIOTECH CO LTD
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