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Immunogenic composition

A technology of immunogenicity and composition, which can be used in drug combinations, antibody medical components, antibacterial drugs, etc., and can solve problems such as inapplicability to humans

Inactive Publication Date: 2011-05-11
ISIS INNOVATION LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Conversely, although CFA elicits a Th1-type immune response in experimental animals, it is not applicable to humans due to the toxic effects caused by excessive inflammatory responses caused by CFA

Method used

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  • Immunogenic composition
  • Immunogenic composition
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Examples

Experimental program
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Effect test

Embodiment 1

[0115] Evaluation of CCR4 Antagonism and Specificity by Chemotaxis Assay

[0116] 116 CCR4 antagonists tested for inhibition of CCR4 + Ability of CCL22-regulated chemotaxis of human Caucasian acute T lymphoblastoid leukemia cell line CCRF-CEM ( figure 2 A). 16 compounds (about 13.7%) inhibited the migration of CCRF-CEM cells regulated by CCR4, IC 50 value (concentration required to inhibit migration by 50%) at 179 x 10 -11 to 229 x 10 -14 within the M range.

[0117] CCRF-CEM can also express another chemokine receptor, CXCR4 ( figure 2 A), which allows the specificity of CCR4 antagonists to be tested. With the exception of one antagonist, compounds had no effect on CXCR4-regulated migration ( figure 2 B) or cell viability (data not shown) had no effect, even at concentrations above their IC 50 value (approximately 2 ) 1000 times.

Embodiment 2

[0119] Disruption of human Treg recruitment regulated by CCL22 and CCL17 by CCR4 antagonists

[0120] Treg negatively regulates immune responses induced by professional antigen-presenting cells. Therefore, inhibiting the CCR4-dependent recruitment of Tregs regulated by CCL22 and CCL17 represents a potential target for promoting immune responses. CD4 expressing high levels of CD25 + CD45RO + Tregs enriched in T cells were isolated from peripheral blood mononuclear cells (PBMC) of healthy donors. These CD4+CD25 高 cells expressed FoxP3 and CCR4 ( image 3 A). In addition, they failed to proliferate and secrete T cell cytokines after in vitro stimulation, and also inhibited the proliferation of co-cultured conventional T cells (data not shown), so it can be confirmed that the isolated CD4+CD25 高 Cells are bona fide Tregs.

[0121] Six compounds (compounds of formula (III), (V), (VI), (VIII), (XI) and (XV)) were tested for their ability to block Treg migration regulated b...

Embodiment 3

[0123] Inhibition of chemotaxis of human Th2 cells regulated by CCL22 and CCL17 by CCR4 antagonists

[0124] Polarized effector T cells are known to influence the development of immune responses. Th2-biased responses can suppress Th1-biased cellular immune responses, which are thought to be more protective against intracellular pathogens (Szabo SJ et al. (2003) Annu Rev Immunol 21:713-758). In addition to Treg, polarized human Th2 cells express CCR4 and migrate in response to CCR4 ligands (Bonecchi R, et al. (1998) J Exp Med 187:129-134). Therefore, it is important to determine whether novel adjuvants can inhibit the migration of polarized Th2 cells, as these cells may be harmful or useful depending on the target pathogen. Figure 4 A demonstrates that polarized Th2 cells generated in vitro can express CCR4. Further, all six CCR4 antagonists significantly inhibited CCL22- and CCL17-directed migration of Th2 cells when observed with Treg ( Figure 4 B, C), and have a...

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Abstract

This invention relates to the use of a CCR4 antagonist as an adjuvant, in particular in an immunogenic composition comprising an antigen which elicits an immune response against a pathogen or tumour.

Description

technical field [0001] The present invention relates to a vaccine adjuvant composition, and relates to the application of the composition in enhancing specific immune response, especially but not limited to the composition in improving human T cell proliferation regulated by dendritic cells. technical background [0002] The development of vaccines with significant induction of cellular responses is a major challenge. T cells are the main effector cells of the cellular immune response. These cells recognize antigens synthesized in pathogen-infected cells, thus successful vaccination requires the synthesis of immunogenic antigens in the cells of the vaccinated individual. One approach is to use live attenuated vaccines, however this approach has significant limitations. For example, there is a risk of infection when the vaccinated individual is immunosuppressed, or when the pathogen itself is capable of inducing immunosuppression (e.g. HIV, HIV). Additionally, some pathoge...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39
CPCA61K39/39A61K2039/55511A61P31/04A61P31/06A61P31/12A61P31/16A61P35/00
Inventor 达伦·劳费尔大卫·F·图赫杰格蒂施·贝瑞马修·N·戴维斯埃尔玛·Z·切尔连
Owner ISIS INNOVATION LTD
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