Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease

a technology of priming, which is applied in the field of ex-vivo priming for generating cytotoxic t lymphocytes specific for non-tumor antigens to treat autoimmune and allergic diseases, can solve the problems of allergic diseases and autoimmune diseases, and achieve the effect of preventing the development and progression of diseases

Inactive Publication Date: 2007-05-03
ORTHO MCNEIL PHARM INC
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016] Immune cells, such as IgE producing B cells and activated CD4 T cells play a central role in the pathogenesis of allergic diseases and autoimmune diseases. The present invention utilizes cytotoxic T lymphocytes (CTLs) to eliminate or inhibit the immune cells that cause the allergy and / or autoimmune diseases. Thus, the development and progression of diseases can be prevented or interrupted by the methods of the present invention.

Problems solved by technology

However, aberrant immune responses can cause allergic diseases and autoimmune diseases.
The current therapies have been focused on the treatment of symptoms of allergy and autoimmune diseases and do not prevent the development and progression of the diseases.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease
  • Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease
  • Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease

Examples

Experimental program
Comparison scheme
Effect test

example 1

Manufacture of Drosophila Antigen-Presenting Cells

[0243] The Schneider S2 cell line was prepared from Drosophila melanogaster (Oregon-R) eggs according to published procedures and has been deposited with the American Type Culture Collection (CRL 10974). S2 cells are grown in commercial Schneider's Drosophila medium supplemented with 10% fetal bovine serum.

[0244] The pRmHa-3 plasmid vector for expressing MHC Class I and co-stimulatory proteins in S2 cells was derived from the pRmHa-1 expression vector constructed as described in the literature. It contains a metallothionein promoter, metal response consensus sequences and an alcohol dehydrogenase gene bearing a polyadenylation signal isolated from Drosophila melanogaster.

Complementary DNAs for Fransfection were Prepared as Follows:

[0245] HLA-A2.1 and β-2 microglobulin: Reverse transcription-PCR from K562 cells using primers derived from the published sequence. [0246] B7.1: Reverse transcription-PCR from K562 cells using primers...

example 2

Trial of Cytotoxic T Cell Infusions Against IgE Producing Cells

Purpose of Trial

[0259] This example teaches the effectiveness of cytotoxic T Cell infusions in the treatment of allergic diseases as assessed according to the following factors: [0260] 1. Safety and toleration of re-infused autologous CTLs after in vitro immunization; [0261] 2. Kinetics of infused CTLs in the systemic circulation factoring in limiting dilution analysis; [0262] 3. Whole body disposition of CTLs by radioscintigraphy; [0263] 4. Cell composition of biopsied nodules by immunohistology (CTLs, TH, NK, B cells); and [0264] 5. Regression of measurable lesions and duration of response over two months.

Treatment with Ex Vivo Generated Autologous CTLs

[0265] All patients will receive, at least, a single infusion of autologous CTLs. The number of cycles and the dose of cells administered to each patient are summarized in Table 1. The number of cells generated in vitro is dependent on patient-related factors such ...

example 3

[0269] IgE plays an essential role in the pathogenesis of allergic asthma. Here, we show that cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. Thus, IgE specific CTL may provide a treatment for allergic asthma and other IgE-mediated allergic diseases.

[0270] Cytotoxic T lymphocytes are derived from resting naïve CD8 T cells. In the present of antigens and co-stimulations, resting naïve CD8 T cells can be activated and differentiated into armed cytotoxic T cells, which can destroy the target cells that express the antigens. CTL...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
temperatureaaaaaaaaaa
timeaaaaaaaaaa
adhesionaaaaaaaaaa
Login to view more

Abstract

Cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTL provides a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptides identified from CD40L can kill activated CD4 T cells. In vitro generated CTL specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo. In contrast, CTL induced by antigenic peptides derived from IgE specifically inhibit IgE responses, and adoptive transfer of CD40L-specific CTL to NOD mice at early age delay the development of diabetes in NOD mice. In vitro generated CTL specific for non-tumor self-antigens expressed on activated CD4 T cells regulate immune responses in vivo.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional application of U.S. application Ser. No. 10 / 144,188, filed May 13, 2002, which claims priority from U.S. provisional application Ser. No. 60 / 291,300, filed May 15, 2001. The disclosures of each of these patent applications are hereby incorporated by reference in their entirety.BACKGROUND OF THE INVENTION [0002] Immune responses to foreign antigens such as those found in bacteria and virus protect from and eliminate infections. However, aberrant immune responses can cause allergic diseases and autoimmune diseases. Immune responses to foreign, sometimes innocuous, substances such as pollen, dust mites, food antigens and bee sting can result in allergic diseases such as hay fever, asthma and systemic anaphylaxis. Immune responses to self-antigens such as pancreatic islet antigens and cartilage antigens can lead to diabetes and arthritis, respectively. The hallmark of the allergic diseases is activation of C...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00C12N5/08C12N15/09A61K35/12A61P3/10A61P11/02A61P11/06A61P17/06A61P19/02A61P25/00A61P29/00A61P37/02A61P37/08C12N5/0783
CPCA61K39/0008A61K2035/122C12N5/0636C12N2501/23C12N2501/51C12N2501/58C12N2502/50C12N2502/99A61P3/10A61P11/02A61P11/06A61P17/06A61P19/02A61P25/00A61P29/00A61P37/02A61P37/06A61P37/08
Inventor CAI, ZELINGJACKSON, MICHAEL R.PETERSON, PER A.SHI, WEI-XINGKONG, YANDEGRAW, JULI
Owner ORTHO MCNEIL PHARM INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap