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

US8106153B2 · kind B2 · utility

Assignee

• Ortho-McNeil Pharmaceutical, Inc. · US

Inventors

• Zeling Cai · San Diego, US
• Michael R. Jackson · Del Mar, US
• Per A. Peterson · Washington, US
• Wei Shi · 安丰镇, CN
• Yan Kong · Montgomery, US
• Juli DeGraw · San Diego, US

Key dates

• Filing date: Sep 28, 2010
• Grant date: Jan 31, 2012
• Expiry date: Sep 28, 2030

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2502/99
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

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 expres…