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A method for enhancing t cell response

一种细胞、免疫增强剂的技术，应用在免疫学和疫苗开发领域，能够解决T细胞弱、疫苗减少抗原模式等问题

Inactive Publication Date: 2014-04-23
MANNKIND CORP
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  • 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

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  • 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

[0100] Mice. 6-12 week old C57BL / 6 mice were purchased from Harlan (Horst, Netherlands). TCR318 transgenic mice were obtained from CytosBiotechnology 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 HLAA2.1 were originally obtained from MannKind Corporation (MannKind Company) (Valencia, CA; Pascolo, S. et al., JExpMed (Journal of Experimental Medicine) 185, 2043-2051, 1997, the entire contents of which are incorporated herein as refer to). Mice were bred and maintained in a specific pathogen-free facility at the University Hospital in Zurich according to the regulations of the Swiss Veterinary Reg...

Embodiment 2

[0113] 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.

[0114] 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 (a total of 125 μg p33 and 12.5 nmol CpG): s1) bolus injection of a single dose on day 0; s2) at day 0 Four equal doses over four days; s3) reduced dose over four days; and s4) increased dose 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...

Embodiment 3

[0124] 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., EurJ Immunol (European Immunology Journal)., 34, 91-97, 2004; Shedlock and Shen, Science (Science), 300, 337-339, 2003; Sun and Bevan, 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 incorporated herein by reference), especially when using strong immunogens, e.g., LCMVgp33. 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-dependence of CTL is very dependent on the experimental condition...

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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] This application is the international application number PCT / US2008 / 002044, the international application date is February 15, 2008, the date of entering the Chinese national phase is October 15, 2009, the Chinese application number is 200880012207.3, and the title of the invention is "for enhancing T cell response method" divisional application. [0002] Cross References to Related Applications [0003] 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 technique [0004] 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 ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61K39/39A61P31/00A61P35/00
CPCA61K2039/55522A61K2039/55577A61K2039/55561A61K2039/5154A61K39/39A61K2039/5152A61K2039/55516A61K39/4634A61K39/464838A61K39/4622A61K39/4611A61K39/4632A61K39/4615A61P31/00A61P31/12A61P35/00A61P37/00A61K2239/31
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
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