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Blockade of tumor-derived ILT4 in adoptive T-cell therapy

A tumor cell and cell technology, applied in the fields of biomedicine and molecular biology, can solve the problem of insignificant clinical benefit of CAR-T treatment

Active Publication Date: 2020-10-27
JINAN CENTER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the clinical benefit of CAR-T therapy in solid tumors is not significant

Method used

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  • Blockade of tumor-derived ILT4 in adoptive T-cell therapy
  • Blockade of tumor-derived ILT4 in adoptive T-cell therapy
  • Blockade of tumor-derived ILT4 in adoptive T-cell therapy

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Experimental program
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Effect test

Embodiment 1

[0047] 1. Cell Culture

[0048] Mouse cell line B16F0 was cultured with RPMI-1640 or DMEM containing 10% FBS and 1% penicillin-streptomycin double antibody; mouse lung cancer cell line MLE12 was cultured with 2% fetal bovine serum, 0.005mg / ml insulin, ITS (1 :100), 10nM hydrocortisone, 10nMβ-estradiol, 2mM L-glutamine in DMEM culture; mouse lung cancer cell line LL / 2 adopts 10% FBS, 2% L-glutamine and 1% Penicillin-streptomycin double-antibody cultured in high-glucose DMEM; MCF10A was cultured in DMEM medium containing 2% fetal bovine serum, 1 μg / ml hydrocortisone, 20ng / ml epidermal growth factor and 1.2 μg / ml insulin; FSK4 was cultured in DMEM medium containing Culture in DMEM with 2% FBS, 1% HEPES solution, 10 μg / ml insulin and 5 ng / ml epidermal growth factor.

[0049] Pmel mouse CD8 + T cells were isolated from mouse spleen cells. After the mice were sacrificed, the spleen was taken out in a sterile environment, gently ground to release the cells, and treated with red bl...

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Abstract

The invention provides an application of blocking tumor-derived ILT4 in adoptive T cell therapy. Researches find that the tumor-derived ILT4 has an induction effect on microenvironment T cell aging, molecular and metabolic mechanisms of the tumor-derived ILT4 are explored in detail, and it is proved from a preclinical model that the targeted ILT4 can reverse the immunosuppressive microenvironmentof tumors and participate in targeted therapy of malignant tumors, and a B6 mouse malignant melanoma adoptive T cell immunotherapy model is further constructed, and the feasibility of ILT4 blocking combined ACT therapy is studied. An effective means is provided for overcoming ACT treatment drug resistance.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and molecular biology, and specifically relates to the application of blocking tumor-derived ILT4 in adoptive T cell therapy. Background technique [0002] The information disclosed in the Background of the Invention is only intended to increase the understanding of the general background of the invention, and is not necessarily to be taken as an acknowledgment or any form of suggestion that the information constitutes the prior art that is already known to those skilled in the art. [0003] The immune system is a natural barrier for the occurrence and development of malignant tumors, among which adaptive T cell immunity plays the most important anti-tumor effect. However, the abundance of infiltrating T cells in the tumor microenvironment is extremely low, and tumor cells can use various mechanisms to induce the non-function of infiltrating T cells, which is one of the main factors for tumor ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P35/00A61P37/04
CPCA61K45/00A61P35/00A61P37/04
Inventor 高爱琴孙玉萍李娟王淑云林文俐王婧男张方
Owner JINAN CENTER HOSPITAL
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