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Enhancer for t-cells or b-cells having memory function, malignant tumor recurrence inhibitor, and inducer for inducing memory function in t-cells or b-cells

A malignant tumor, B cell technology, applied in receptors/cell surface antigens/cell surface determinants, medical preparations containing active ingredients, antitumor drugs, etc., can solve the loss of function, side effects, unclear recurrence of malignant tumors and other problems to achieve the effect of inhibiting recurrence

Pending Publication Date: 2020-05-15
YAMAGUCHI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are various problems such as side effects, loss of some functions, inability to treat recurrence or metastasis, etc.
This method can enhance the activation of endogenous immunocompetent cells in the host (recipient) and the ability to accumulate to tumor cells. However, it is not clear whether the use of this immunocompetent cell therapy can prevent recurrence for a long time etc. Persistent rejection of malignancy

Method used

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  • Enhancer for t-cells or b-cells having memory function, malignant tumor recurrence inhibitor, and inducer for inducing memory function in t-cells or b-cells
  • Enhancer for t-cells or b-cells having memory function, malignant tumor recurrence inhibitor, and inducer for inducing memory function in t-cells or b-cells
  • Enhancer for t-cells or b-cells having memory function, malignant tumor recurrence inhibitor, and inducer for inducing memory function in t-cells or b-cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0149]

[0150] In order to investigate the anti-tumor effect of CAR-IL-7 / CCL19 expressing T cells, it was investigated whether endogenous T cells derived from the same host (recipient) as the administered donor T cells infiltrated in the tumor tissue. tumor tissue. First, 2.5×10 6 3LL-hCD20 (3LL derived from mouse lung cancer cells genetically recombined to express human CD20) (day 0). On the 7th day thereafter, cyclophosphamide (CPA: 100 mg / kg) as an anticancer agent was intraperitoneally administered. On day 10, positive CD90.1 (CD90.1 + ), CD90.2 negative (CD90.2 - ) 1×10 generated from congenic mice 6 The above-mentioned anti-human CD20 CAR-expressing T cells, the above-mentioned anti-human CD20 CAR-IL-7 / CCL19-expressing T cells, or the above-mentioned isolated mouse T cells without gene introduction were administered intravenously. On day 19, tumor tissues were removed from the mice. For primary staining, a biotin-labeled anti-CD90.1 antibody (cloneOX-7 BioLegend...

Embodiment 2

[0153]

[0154] C57BL / 6 mice were subcutaneously inoculated with 2.5×10 6 3LL-hCD20 (day 0). On day 3 thereafter, positive CD90.1 (CD90.1 + ), CD90.2 negative (CD90.2 - ) 1×10 generated from congenic mice 6 Anti-human CD20 CAR-expressing T cells (Conventional: Conv.) or anti-human CD20 CAR-IL-7 / CCL19-expressing T cells (7×19) were administered intravenously. The antibody against CD90.2 (Thy1.2) expressed in endogenous T cells, that is, anti-CD90.2 antibody (anti-CD90.2: it is a hybridoma purchased from ATCC by the inventors of the present application (hybridoma)) was administered intraperitoneally twice a week from day 1. The dose was set to 1 mg / mouse for the first two doses, and 0.5 mg / mouse thereafter. The mean±SD of tumor volume on day 14 of each group (n=5) is shown in figure 2 . ○ represents the value of each mouse.

[0155] like figure 2 As shown, in the case of administration of anti-human CD20 CAR-IL-7 / CCL19 expressing T cells, the proliferation of malign...

Embodiment 3

[0157]

[0158] In terms of the acquisition of memory functions of donor CAR-T cells and endogenous T cells based on anti-human CD20 CAR-IL-7 / CCL19 expressing T cells, and the increase of cells with memory functions, the use of memory cells The markers of CD44 as well as CD62L were evaluated.

[0159] C57BL / 6 mice were subcutaneously inoculated with 2.5×10 6 3LL-hCD20 (day 0). On day 3 thereafter, positive CD90.1 (CD90.1 + ), CD90.2 negative (CD90.2 - ) 1×10 generated from congenic mice 6 The above anti-human CD20 CAR-expressing T cells (Conv.) or the above-mentioned anti-human CD20 CAR-IL-7 / CCL19 expressing T cells (7×19) were administered intravenously. On day 28, spleen cells were harvested for the following analysis.

[0160] Donor T cells were used as CD90.1 positive cells (CD90.1 + ), the recipient T cells were identified as CD90.2 positive cells (CD90.2 + ) and identified. Expression of memory T cell markers (CD44 and CD62L) and CAR in CD4-positive and CD8-pos...

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PUM

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Abstract

The purpose of the present invention is to provide, in order to continue the rejection of malignant tumors over a long period of time, an enhancer for endogenous T-cells or B-cells having a memory function, and a malignant tumor recurrence inhibitor. The present invention involves preparing: an enhancer for subject T-cells or B-cells having a memory function, said enhancer including a nucleic acidtransportation medium, a nucleic acid encoding interleukin 7 (IL-7) and a nucleic acid encoding chemokine (C-C motif) ligand 19 (CCL 19); an inducer which induces the memory function in the T-cells or B-cells in a subject; and a malignant tumor recurrence inhibitor which includes a nucleic acid transport medium, a nucleic acid encoding interleukin 7 (IL-7) and a nucleic acid encoding CCL19.

Description

technical field [0001] The present invention relates to administering to a subject an enhancer of T cells or B cells with memory function, an inhibitor of recurrence of malignant tumors, and an inducer of memory function to T cells or B cells administered to a subject, the above-mentioned reagents comprising nucleic acid delivery Medium, nucleic acid encoding interleukin 7 (Interleukin-7: IL-7), and nucleic acid encoding chemokine (C-C motif) ligand 19 (chemokine (C-C motif) ligand 19: CCL19). Background technique [0002] Malignant tumors are diseases that affect a large number of patients worldwide, and chemotherapy, radiation therapy, or surgical treatment is generally performed extensively. However, there are various problems such as occurrence of side effects, loss of a part of function, inability to treat recurrence or metastasis, and the like. Therefore, in order to maintain a higher quality of life (QOL) of patients, the development of immune cell therapy has been p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K9/51A61K35/17A61K35/28A61K35/74A61K35/768A61K48/00A61P35/00C12N5/0781C12N5/0783C12N15/24A61K38/19A61K38/20
CPCA61K39/464421A61K39/4632A61K39/46444A61K39/464499A61K39/464468A61K39/4631A61K39/4611A61K39/464424A61K9/127A61K9/51A61K48/00A61P35/00C07K2319/03C07K14/7051A61K38/20A61K38/195Y02A50/30A61K35/768A61K2239/31A61K2239/38A61K35/17A61K2039/5156A61K35/74A61K48/0008A61K35/60A61K2039/5158A61K35/76A61K38/2046A61K35/28A61K38/19A61K39/0011C07K14/521C07K14/5418
Inventor 玉田耕治佐古田幸美安达圭志中村贵史
Owner YAMAGUCHI UNIV
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