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Pretreatment drug for t cell infusion therapy for immune-checkpoint inhibitor-resistant tumor

A technology of immune checkpoints and inhibitors, applied in the direction of anti-tumor drugs, drug combinations, drug delivery, etc., can solve the problem of small effect and achieve the effect of enhancing anti-cancer effect

Pending Publication Date: 2018-10-23
MIE UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is a possibility that these treatments will have little effect on tumors that do not express the target molecule of the immune checkpoint inhibitor

Method used

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  • Pretreatment drug for t cell infusion therapy for immune-checkpoint inhibitor-resistant tumor
  • Pretreatment drug for t cell infusion therapy for immune-checkpoint inhibitor-resistant tumor
  • Pretreatment drug for t cell infusion therapy for immune-checkpoint inhibitor-resistant tumor

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Experimental program
Comparison scheme
Effect test

Embodiment 2

[0077] 1. Materials and Methods

[0078] Anti-mouse CTLA-4 antibody (clone 9D9) was produced by Mie University using a hybridoma donated by Dr. James P. Allison of MD Anderson Cancer Center. Anti-mouse GITR antibody (clone DTA-1) was produced by Mie University using a hybridoma donated by Dr. Shifumi Sakaguchi of Osaka University. As the anti-mouse PD-1 antibody (clone RMP1-14), an antibody donated by Dr. Hideo Yagida of Juntendo University was used. Fetal bovine serum (FBS) was purchased from BioWest. RPMI1640 medium (with 2-mercaptoethanol added) was purchased from the Institute of Cell Science. As the mouse colorectal cancer CT26 cell line (CRL-2638), a cell line purchased from ATCC and passaged by Mie University was used. As the mouse fibrosarcoma CMS7 cell line and the mouse fibrosarcoma CMS5a cell line, cell lines obtained from Memorial Sloan Kettering Cancer Institute and passaged by Mie University were used. The human NY-ESO-1 antigen gene was a gift from Memorial ...

Embodiment 3

[0083] 1. Materials and Methods

[0084] Cholesterol pullulan (CHP for short, trade name CHP-80T) was obtained from NOF Corporation. Incomplete Freund's adjuvant (abbreviated as IFA, model F5506) was purchased from Sigma Aldrich. Long-chain peptide antigen-loaded CHP nanogels were prepared as follows. The long-chain peptide antigen chemically synthesized by Bio-Synthesis (MEN peptide: SNPARYEFLYYYYYYQYIHSANVLYYYYYYRGPESRLL (sequence number 1) or p121 peptide: NDHIAYFLYQILRGLQYIHSANVLHRDLKPSNLLLNT (sequence number 2)) was dissolved in dimethyl sulfoxide (DMSO, Nacalai for short) at a concentration of 10 mg / mL Tesque). CHP was dissolved in phosphate-buffered saline (PBS) containing 6M urea (Nacalai Tesque) at a concentration of 10 mg / mL. 1 mL (10 mg) of the long-chain peptide antigen solution and 20 mL (200 mg) of the CHP solution were mixed, and left overnight at 4°C in the dark while stirring gently. The mixed solution was transferred to a dialysis membrane (molecular weig...

Embodiment 4

[0093] 1. Materials and Methods

[0094] Rhodamine-labeled CHP nanogels were donated by Dr. Kazushige Akiyoshi, Kyoto University. APC-Cy7-labeled anti-mouse CD45 antibody (clone 30-F11), FITC-labeled anti-mouse CD8 antibody (clone 53-6.7), PE-labeled anti-mouse CD11b antibody (clone M1 / 70), Pacific blue-labeled anti-mouse F4 / 80 antibody (clone BM8) and PE-Cy7 labeled anti-mouse CD11c antibody (clone N418) were purchased from BioLegend. PerCP-Cy5.5 labeled anti-mouse CD4 antibody (clone RM4-5) was purchased from BD Bioscience. APC-labeled anti-mouse B220 antibody (clone RA3-6B2) was purchased from eBioscience. Fetal bovine serum (FBS) was purchased from BioWest. RPMI1640 medium (supplemented with 2-mercaptoethanol) was purchased from the Institute of Cell Science. Red blood cell hemolysis solution (0.15M NH 4 Cl / 10mM KHCO 3 / 0.1mM EDTA.Na 2 pH 7.2) produced by Mie University. As the mouse fibrosarcoma CMS5a cell line, a cell line donated by Memorial Sloan Kettering Canc...

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Abstract

To provide a technique relating to a therapy for an immune-checkpoint inhibitor-resistant tumor. The problem can be solved by a pharmaceutical composition which is intended to be administered prior tothe administration of T cells specific to an antigen in a T cell infusion therapy for an immune-checkpoint inhibitor-resistant tumor, said pharmaceutical composition containing an antigen-encapsulated nano gel, wherein the antigen-encapsulated nano gel comprises a long-chain peptide antigen or a protein antigen each of which is encapsulated in a hydrophobized polysaccharide nano gel, and the long-chain peptide antigen or the protein antigen contains a CD8-positive cytotoxic T cell-recognizing epitope and a CD4-positive helper T cell-recognizing epitope both originated from the aforementionedantigen.

Description

technical field [0001] The present invention relates to pretreatment agents that enhance the effect of T cell infusion therapy on immune checkpoint inhibitor resistant tumors. Background technique [0002] T cells play an important role in tumor immune response. T cells recognize the major histocompatibility gene complex (MHC) on the cell surface as antigen-presenting cells (dendritic cells, macrophages, etc.) ) The epitope peptide from the antigenic protein presented by the complex. This response is called antigen stimulation. Simultaneously with antigen stimulation, co-stimulatory signals are established through the binding of membrane protein CD28 present on the surface of T cells and membrane protein CD80 or CD86 on antigen-presenting cells. The TCR signal stimulated by the antigen and the co-stimulatory signal are simultaneously input, whereby T cells are properly activated. [0003] On the other hand, there is a control mechanism called an immune checkpoint so that...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A01K67/027A61K9/14A61K35/17A61K45/00A61K47/36A61P35/00A61P37/04A61P43/00C07K14/00
CPCA61K45/06A61K9/5161A61K9/0019A01K2267/0331A01K2227/105A01K2207/12A61K39/00A61P35/00A61K2239/31A61K39/4611A61K39/464462A61K39/4632A01K67/027A61K9/14A61K45/00A61K47/36C07K14/00
Inventor 珠玖洋原田直纯村冈大辅秋吉一成
Owner MIE UNIVERSITY
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