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Inhibition of graft versus host disease

A technology for bone marrow transplantation and patients, which is applied to the preparation of this component substance, which is given to patients in the field of oxidative stress in vitro, which can solve the problems of not being able to save the lives of patients, and achieve the effect of reducing risks and preventing failure and infection

Inactive Publication Date: 2001-09-26
VASOGEN IRELAND LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As a result, current approaches to treating GVHD have been successful only in limited donor-host combinations, preventing effective life-saving therapy for many patients

Method used

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  • Inhibition of graft versus host disease
  • Inhibition of graft versus host disease
  • Inhibition of graft versus host disease

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0035] Splenocytes from C57B1 / 6J (B6) mice were suspended in α-MEM, 2ME, and 10% fetal calf serum (FCS) to a density of 10 7 / ml. FCS contains cytokines and growth factors. The cell suspension was irradiated by UV-C lamp with a wavelength of 253.7nm at 42.5°C, while the mixed gas of 14-15mcg / ml ozone / medical grade oxygen bubbled through the suspension. Treatment was carried out for 3 minutes.

[0036] Immediately after treatment, the cells were only about 10% viable. Example 2

example 2

[0037] The experiment of Example 1 was essentially repeated except that the cells were suspended in 100% FCS. In this case, the immediate survival of the cells was 50-60%, indicating that the factors present in the FCS are protective for at least some of the cells. Example 3

example 3

[0038] B6 murine splenocytes suspended in 100% FCS were subjected to UV-oxidation-heat treatment. At 42.5°C, the cell suspension was irradiated by a UV-C lamp with a wavelength of 253.7nm, while a mixed gas of 14-15mcg / ml ozone / medical grade oxygen bubbled through the suspension. Treatment was carried out for 3 minutes. Different amounts were injected into sublethally irradiated CB-17 SCID mice. Their subsequent performance was compared to those receiving the same number of untreated B6 splenocytes.

[0039] Figure 1 is a graphical illustration of the results of these experiments, where the % survival of animals in each group is plotted on the ordinate against the number of days after injection of treated and untreated cells. Survival was significantly improved at all dose levels when treated cells were used relative to untreated cells, showing the potential of the method of the invention to alleviate GVHD.

[0040] Figure 2 is a plot of the number of cells per spleen donor...

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Abstract

The development of graft versus host disease in a mammalian patient undergoing cell transplantation therapy for treatment of a bone marrow mediated disease, is prevented or alleviated by subjecting at least the T-cells of the allogeneic cell transplantation composition, extracorporeally, to oxidative stress, in appropriate dosage amounts, such as bubbling a gaseous mixture of ozone and oxygen through a suspension of the T-cells. The process may also include irradiation of the cells with UV light, simultaneously with the application of the oxidative stress. The oxidative stress induces reduced inflammatory cytokine production and a reduced proliferative response in the T-cells.

Description

[0001] scope of invention [0002] The present invention relates to a cell component for medical treatment, a method for its preparation and its use in medical treatment. More particularly, the invention relates to cellular components useful in alleviating complications following allogeneic bone marrow transplantation known as graft-versus-host disease in mammalian patients, particularly human patients, and to the preparation of such method of composition. Background of the invention [0003] Bone marrow transplantation, BMT, is necessary after the bone marrow has been damaged. For example, the bone marrow is the first target organ to fail after broad body irradiation or chemotherapy. Metastatic cancer is usually given very high doses of chemotherapy, which kills the cancer cells but also effectively destroys the bone marrow. This requires BMT. Leukemias are myeloid malignancies and are usually treated with BMT after eradication of malignant cells with chemotherapy and / or ...

Claims

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Application Information

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IPC IPC(8): C12N5/02A61K35/17A61K35/28A61P35/02A61P43/00C12N5/0783
CPCA61K35/17C12N5/0636A61K41/0019Y10S424/81C12N2500/05C12N2500/02A61K35/28A61K41/17A61P35/02A61P37/06A61P43/00A61K39/46434A61K39/4621A61K39/4611A61K2300/00C12N5/00
Inventor D·E·斯潘内
Owner VASOGEN IRELAND LTD
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