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Educated NKT cells and their uses in the treatment of immune-related disorder

An NKT cell, immune-related technology, applied in the field of educated NKT cells and their use in the treatment of immune-related disorders, can solve the problem that the precise mechanism has not yet been discovered.

Inactive Publication Date: 2004-04-14
ENZO THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this procedure is well established as a method of immune tolerance induction, the precise mechanism has not been discovered

Method used

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  • Educated NKT cells and their uses in the treatment of immune-related disorder
  • Educated NKT cells and their uses in the treatment of immune-related disorder
  • Educated NKT cells and their uses in the treatment of immune-related disorder

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0245] Tolerance induction in experimental colitis

[0246] To assess the role of tolerance induction in the experimental colitis model, six groups of mice consisting of 20 animals each were studied (Table 1). All mice were rectally challenged with TNBS (groups A, B, D and E) or normal saline (control groups C and F) on day 1 of the study. From the day of colitis induction, mice of all groups were fed every other day for 11 days (50 μg / mouse). Groups B and E included mice fed with colitis-extracted protein (CEP). Mice in groups A, C, D and F were supplied with bovine serum albumin (BSA, 50 μg / mouse). All groups of mice were sacrificed 14 days after colitis induction. Mice in groups D-F were treated with anti-NK1.1 anti-mouse monoclonal antibody 36 hours before study termination as described above. Mice in groups A-C were not NK1.1-null.

[0247]Table 1

[0248] Group

NK1.1 deletion

supplied antigen

rectal stimulation

A

-

BSA

TNBS...

Embodiment 2

[0259] NK1.1+ lymphocytes have increased CD4+IL4+ / CD4+IFNγ+ ratio in tolerized mice and decreased CD4+IL4+ / CD4+IFNγ+ ratio in non-tolerized mice with experimental colitis

[0260] Tolerized mice

[0261] To study the role of NK1.1+ lymphocytes in tolerized mice, splenocytes and liver-associated lymphocytes (2.5 × 10 6 Splenocytes and 0.5 x 10 6 LAL) and cultured for 72 hours in the presence of CEP and APC. Flow cytometry analysis showed that NK1.1-deficient concomitant oral tolerance-induced decreased CD4+IL4+ / CD4+IFNγ+ ratio compared to non-NK1.1 LAL-depleted tolerized mice (in E and 0.99±0.03 vs. 1.8±0.35 CD4+IL4+ / CD4+IFNγ+ in group B, p figure 2 ). The control NK1.1-deleted group (Group F) revealed a decrease in the CD4+IL4+ / CD4+IFNγ+ ratio compared to the non-NK1.1-deleted group C (2.13±0.36 vs. 1.6±0.29 for C and F groups, respectively ).

[0262] non-tolerized mice

[0263] In contrast to the tolerized group, NK1.1-deletion had the opposite effect on non-tolerized ...

Embodiment 3

[0266] Effects of in vitro sensitization and effect of disease-directed antigens on the ratio of CD4+IL4+ / CD4+IFNγ+ in tolerized and non-tolerized mice with experimental colitis

[0267] To assess the effect of ex vivo exposure to disease-directed antigens on the CD4+IL4+ / CD4+IFNγ+ ratio, splenocytes and liver-associated lymphocytes (2.5 × 10 6 ) splenocytes and (0.5×10 6 ) LAL and cultured for 12 hours in the presence of Con A but in the absence of CEP and APC. Assessments of the effects of NK1.1 deletion in the absence of antigen were similar to those found in the presence of antigen. Lymphocytes harvested from tolerized mice in group B revealed significantly higher CD4+IL4+ / CD4+IFNγ+ ratios compared to NK1.1-null mice in tolerized group E (0.7 ± 0.02 vs. 1.1±0.02, p Figure 5 ). These results suggest that immune training is achieved in vivo and is not affected by cell-antigen incubation in vitro.

[0268] Similarly, flow cytometry analysis showed that the ratio of CD4+IL...

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PUM

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Abstract

The present invention relates to a method for the treatment of immune-related disorders in a mammalian subject in need of such treatment. This method comprises the step of manipulating the NK T cell population in said subject by suitable means, said manipulation of the NK T cell population resulting in modulation of the Th1 / Th2 balance toward anti-inflammatory cytokine producing cells. Manipulation of the NK T cell population may be performed either by depletion of said cells by a suitable means or alternatively by ex vivo education of the NK T cells, such that the educated NK T cells have the capability to modulate the Th1 / Th2 balance toward anti-inflammatory cytokine producing cells. The invention further relates to pharmaceutical compositions for the treatment of immune-related disorders in a mammalian subject. These compositions comprising as an effective ingredient an ex vivo educated NK T cell. The invention further provides for an ex vivo educated NK T cell and uses thereof in the treatment of immune-related disorders.

Description

field of invention [0001] The present invention relates to the field of therapeutic methods, compositions and their use in the treatment of immune-related disorders in mammalian subjects. More specifically, the methods and compositions of the invention relate to the treatment of NK T cell populations in a subject that results in the regulation of Th1 / Th2 cell balance in favor of anti-inflammatory cytokine producing cells and their involvement in intestinal and immune Use in the treatment of related diseases and malignant tumors. [0002] All patents, patent applications, patent publications, scientific papers, etc. cited or identified in this application are hereby incorporated by reference in their entireties in order to more fully describe the state of the art to which this application pertains. Background of the invention [0003] The immune system is responsible for a major part of the defense against potentially harmful agents. However, this system can become hostile ...

Claims

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Application Information

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IPC IPC(8): A61K35/14A61K35/17A61K38/19A61K39/00C12N5/0783
CPCA61K35/17C07K16/2803A61K39/0008C12N5/0646C12N5/0087A61K2039/5158A61K2039/577C12N2502/1114A61K2039/542A61P1/00A61P35/00A61P37/00A61P37/02A61K39/4621A61K39/4644A61K2239/53A61K39/461A61K39/4613A61K39/46433A61K2239/38A61K2239/31
Inventor Y·伊兰
Owner ENZO THERAPEUTICS
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