Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A method for enhancing t cell response

A technology of cells and cytokines, applied in the field of immunology and vaccine development, can solve problems such as weak T cells and reduced antigenic patterns of vaccines

Inactive Publication Date: 2010-02-24
MANNKIND CORP
View PDF29 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

While live vaccines produced increased antigen doses that elicited strong immune responses, non-replicating vaccines produced a reduced antigenic pattern that, as demonstrated in the Examples herein, was a rather weak stimulator of T cells

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
  • A method for enhancing t cell response
  • A method for enhancing t cell response
  • A method for enhancing t cell response

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

Example 1: Materials and methods

[0091] Mice. 6-12 week old C57BL / 6 mice were purchased from Harlan (Horst, Netherlands). TCR318 transgenic mice were obtained from Cytos Biotechnology AG (Schlieren, Switzerland), which express a T-cell receptor specific for the peptide gp33 (aa33-41), which represents the bPredominant immune epitope of lymphocytic choriomeningitis virus (LCMV) located in glycoprotein in mouse (Pircher, H., et al. 1989. Nature (natural) 342:559-561; Pircher, H. . et al., Nature 346, 629-633, 1990, each of which is incorporated herein by reference in its entirety). HHD transgenic mice expressing HLA A2.1 were initially obtained from MannKind Corporation (MannKind Company) (Valencia, CA; Pascolo, S. et al., J Exp Med (Journal of Experimental Medicine) 185, 2043-2051, 1997, the entire content of which incorporated herein by reference). Mice were bred and maintained in a specific pathogen-free facility at the University Hospital in Zurich according to the regul...

Embodiment 2

[0103] It was investigated whether T cell responses could be enhanced by increasing antigen stimulation. In the first experiment, the 1x10 6 Transgenic gp33-specific T cells were transferred into C57BL / 6 wild-type recipient mice to increase the frequency of precursor T cells and facilitate the assessment of immune responses.

[0104] use figure 1 D and different vaccination schemes disclosed in Table 1, all mice were immunized with the same cumulative dose of gp33 peptide mixed with CpGODN (total 125 μg gp33 and 12.5 nmol CpG): s1) single dose bolus injection on day 0; s2 ) four equal doses over four days; s3) reduced doses over four days; and s4) increased doses over four days. In addition, groups of mice were immunized with a single dose of CpG followed by exponentially increasing doses of the gp33 peptide (s5), or with a single dose of gp33 followed by exponentially increasing doses of CpG (s6). Mice infected intravenously with 250 pfu of LCMV virus on day 0 served as po...

Embodiment 3

Example 3: CD8 + Enhancement of T cell responses independent of T cell helper

[0111] with CD8 + The role of T-helper in relation to T cell priming is well known in the art. Th epitope may be responsible for functional CD8 + T cell immunity is critical (Johansen et al., Eur J Immunol., 34, 91-97, 2004; Shedlock and Shen, Science, 300, 337-339, 2003; Sun and Bevan , Science (Science), 300, 339-342, 2003, each of which is incorporated herein by reference in its entirety). On the other hand, in the case of high precursor frequency, CD8 + T cell responses are less Th-dependent (Mintern et al., J Immunol., 168, 977-980, 2002, the entire contents of which are hereby incorporated by reference), especially when using strong immunogens such as , LCMV gp33. Furthermore, the route of administration can also affect the requirement for T-help (Bour et al., J Immunol., 160, 5522-5529, 1998, the entire contents of which are incorporated herein by reference). Therefore, the Th-dependen...

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

No PUM Login to View More

Abstract

Embodiments of the invention disclosed herein relate to methods and compositions for exponentially increasing antigenic stimulation of class I MHC CD8<+> T cell responses over that based in the art. Some embodiments relate to an immunogenic composition that enhances an immune response in a subject. In some embodiments, the immunogenic composition comprises an antigen in combination with an immunopotentiator or a biological response modifier (BRM). Overall, the invention disclosed herein demonstrates that increasing antigenic stimulation in a manner independent of the dose of the antigen enhances immunogenicity.

Description

[0001] Cross References to Related Applications [0001] This application claims priority to US Provisional Application Serial No. 60 / 901,980, filed February 15, 2007, which is hereby incorporated by reference in its entirety. Background of the invention [0002] Embodiments of the invention relate to the fields of immunology and vaccine development. Embodiments of the invention disclosed herein relate to methods and compositions for boosting immunization and vaccination. More specifically, embodiments of the invention relate to methods of increasing T cell responses to stimulation. Some embodiments of the invention have further application as vaccination strategies in the treatment of diseases such as infectious diseases or cancer. background [0003] Live attenuated vaccines usually induce strong and long-lasting immune responses after a single injection, and many viral vaccines of this type have potencies in excess of 90% (Nossal, G. Vaccines in Fundamental Immunology (...

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
IPC IPC(8): A61K39/00A61K39/145
CPCA61K2039/55522A61K2039/55577A61K2039/55561A61K2039/5154A61K39/39A61K2039/55516A61K2039/5152A61P31/00A61P31/12A61P35/00A61P37/00A61K2239/31A61K39/4634A61K39/464838A61K39/4622A61K39/4611A61K39/4632A61K39/4615
Inventor 托马斯·昆迪希阿德里安·博特肯特·安德鲁·史密斯裘志勇
Owner MANNKIND CORP
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products