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Immune-tolerance inducer

A technology of immune tolerance and inducer, which is applied in the direction of immunoglobulin, drug combination, antibody, etc., to achieve the effect of promoting effective induction

Inactive Publication Date: 2015-12-02
REGIMMUNE CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is still no report on the control of transplant immunity obtained through the combined use of NKT cell activation and CB

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0118] Example 1. Bone marrow transplantation and preparation of bone marrow chimeras

[0119] 8-12 weeks old male mice C57BL / 6NCrSlc(B6,H-2 b ), BALB / cCrSlc (BALB / c, H-2 d ) and C3H / HeSlc (C3H,H-2 k ) was purchased from Japan Slc, Inc. Mice were maintained under the SPF environment at the Laboratory Animal Research Institute of Tokyo Women's Medical University according to the animal care guidelines of the NIH.

[0120] Recipient BALB / c mice were irradiated with TBI (total body irradiation) 3 Gy (X-ray generator MBR-1520R-3, Hitachimedical Corp., Tokyo, Japan) 2-3 hours before bone marrow transplantation. Then, the anti-CD40L antibody was diluted with PBS (Invitrogen, Grand Island, NY, USA), and 0.5 mg of the anti-CD40L antibody was intraperitoneally administered immediately after the bone marrow transplantation. Anti-CD40L antibody was purchased from Bixcell (West Lebanon, NH, USA). And, the KRN7000-containing liposome obtained by the same method as in WO2005 / 120574 (cont...

Embodiment 2

[0134] Example 2. Heart transplantation

[0135] Fourteen days after the bone marrow transplantation of the TBI+anti-CD40L+KRN7000-containing liposome group and the TBI anti-CD40L group in Example 1, heterotopic heart transplantation was performed from the same donor as the bone marrow donor (B6 mice). Donor and recipient mice were anesthetized by intraperitoneal administration of pentobarbital (DainipponSumitomoPharma, Osaka, Japan). The donor mouse was cut from its abdomen, and 1% heparin saline was injected from the abdominal aorta to perfuse the blood, and then a thoracotomy was performed on the mouse, and the heart was excised. The recipient mouse was cut open from its abdomen, and the ascending aorta and pulmonary artery of the donor heart were anastomosed end-to-side to the abdominal aorta and vena cava, respectively, using 10-0 nylon sutures. After the operation, the beat of the transplanted heart in the abdomen was determined manually, and when the beat could not be ...

Embodiment 3

[0139] Example 3. Assessment of Cytokine Production and Regulatory T Cells Following Bone Marrow Transplantation

[0140] Serum cytokine (IL-2, IL-4, IL-10, IL-12 and IFN-γ) values ​​were measured at 2 hours, 24 hours and 48 hours after bone marrow transplantation in each group in Example 1. The results are shown in Figure 8-12 middle.

[0141]In the TBI+anti-CD40L group, IL-10 was slightly elevated 2 hours after transplantation, but much lower compared to those in the TBI+anti-CD40L+KRN7000-containing liposome group and TBI+KRN7000-containing liposome group. However, these cytokines subsided 24 hours after transplantation. In TBI+anti-CD40L+KRN7000-containing liposome group and TBI+KRN7000-containing liposome group, IL-12 also increased rapidly after transplantation. While IL-12 production was enhanced after 24 hours in the TBI+liposomes containing KRN7000 group, IL-12 subsided after 24 hours in the TBI+anti-CD40L+liposomes containing KRN7000 group. In the TBI+KRN7000-co...

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Abstract

The purpose of the present invention is to create an immune tolerance-inducing agent used in therapy in which donor hematopoietic cells are transplanted into a recipient in order to induce immune tolerance in the recipient with respect to donor cells, tissue, or organs. By using an alpha-galactosylceramide-containing liposome in combination with a costimulatory-pathway-blocking substance, hematopoietic chimerism can be induced in the recipient by transplantation of donor hematopoietic cells, making it possible to induce immune tolerance in the recipient with respect to donor cells, tissue, or organs.

Description

technical field [0001] The present invention relates to immune tolerance inducing agents for use in therapy in which donor hematopoietic cells are transplanted into a recipient to induce immune tolerance in the recipient to the donor cells, tissues or organs. Background technique [0002] Organ transplantation is considered the final and only cure for many organ failures. The control of many acute rejections of transplanted organs has become possible due to the development and advancement of immunosuppressants. On the other hand, the long-term survival rate of transplanted organs is still not good due to the toxicity of long-term administration of immunosuppressants or chronic rejection that is difficult to control with current immunosuppressants. Induction of transplant tolerance aims to allow the immune system of organ transplant recipients to recognize the transplanted organ as self, and it is thought that once immune tolerance is induced, it is possible to significantly...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7032A61K9/127A61K39/395A61K45/00A61P37/06A61P43/00
CPCA61K39/3955A61K9/127A61K9/1272A61K31/7032A61K39/395A61K45/00A61K45/06A61P37/06A61P43/00C07K16/2875A61K2300/00
Inventor 平井敏仁尾本和也田边一成川口绘美石井保之森田晴彦
Owner REGIMMUNE CORP
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