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Chlamydia-activated B cell platforms and methods thereof

A technology of B cells and chlamydia, which is applied in the direction of chlamydia antigen components, animal cells, non-animal cells, etc., and can solve problems such as inapplicability to clinical applications

Pending Publication Date: 2017-09-26
OHIO STATE INNOVATION FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although B cells have been described to induce T cell tolerance or even block antitumor immune responses in vivo, these reports were limited to resting B cells that lack the expression of important helper and co-stimulatory molecules
On the other hand, B cells can be activated to become efficient APCs by a combination of CD40L-expressing cells and cytokines or Toll-like receptor (TLR) ligands, however these approaches do not induce optimal B-cell activation (TLR ligands) or require the use of cell lines (CD40L), and these limitations make them unsuitable for clinical use

Method used

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  • Chlamydia-activated B cell platforms and methods thereof
  • Chlamydia-activated B cell platforms and methods thereof
  • Chlamydia-activated B cell platforms and methods thereof

Examples

Experimental program
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Embodiment 1

[0112] Example 1: Methods of making and using Chlamydia-activated B cells

[0113] B cells for use with the methods and platforms disclosed herein can be obtained from a variety of sources, including monocytes from peripheral blood and primary and secondary lymphoid organs such as bone marrow and lymph nodes, respectively. For example, in humans, B cells make up approximately 1% to 15% of total peripheral blood leukocytes, 20% to 25% of lymph node cells, and up to 50% of spleen cells. If desired, the frequency of B cells can be expanded in vivo by administering appropriate cytokines and recruitment growth factors (eg, IL-4, GM-CSF, and IL-3) to the patient prior to obtaining peripheral blood. Mononuclear cells are obtained from these tissues, e.g., from peripheral blood using density gradient centrifugation, while lymph node cells can be isolated from intact tonsils, e.g., by mincing the tissue and then obtaining a single cell suspension by straining . Preferably, monocyte...

Embodiment 2

[0116] Example 2: Method of Conjugating Antigens to Chlamydia Activated B Cells

[0117] CAB was prepared as shown in Example 1. Fresh or frozen CABs can be conjugated or cross-linked with the desired antigen (protein or peptide) just prior to administration to the subject. Conjugation or crosslinking can be performed, for example, using the zero-length crosslinker 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDAC). The CAB was washed with PBS (pH 6.0) and washed with 2 × 10 8 / ml resuspension, then EDAC was added to the cell suspension, followed by the addition of sufficient concentration of antigen (protein or peptide), mixed well and incubated at 4°C for 1 hour. After incubation, the antigen-crosslinked cells are washed with PBS (pH 7.4) and can be further processed or can be prepared for administration. This procedure can be performed regardless of the source of the CAB (autologous or allogenic). Other types of crosslinkers can be used, depending on the nature of ...

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Abstract

Disclosed herein is a Chlamydia-activated B cell (CAB) platform. Also disclosed is a method of enhancing a population of B cells, comprising exposing said B cells to Chlamydia spp. under conditions suitable to enhance the population of B cells, such that expansion and differentiation of said B cells takes place, and said B cells are exposed or crosslinked to an antigen. Also disclosed are methods of producing said CABs, and treating a subject in need thereof with said CABs.

Description

[0001] Cross references to related patent applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 114,349, filed February 10, 2015, and U.S. Provisional Application No. 62 / 247,827, filed October 29, 2015, both of which are incorporated by reference in their entirety into this article. Background technique [0003] Dendritic cells (DCs) are considered potent antigen-presenting cells (APCs) and potent inducers of protective immunity against infectious diseases and cancer. These have sparked intense interest in the use of DCs as cellular vaccines, especially DCs differentiated to form peripheral blood mononuclear cells. However, overall clinical response rates demonstrated by clinical trials using DCs are very low, emphasizing the need for improved DC-based vaccines. A particular limitation to the success of these cell therapies is the limited number of DCs that can be generated from monocytes because DCs cannot be expanded ex vivo, maki...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P37/04C12N5/0781A61K39/118
CPCC12N5/0635A61K2039/58A61K2039/6006C12N2500/72C12N2502/70A61K39/118A61P31/00A61P31/04A61P35/00A61P37/04A61P43/00A61K39/4612A61K39/4622A61K2239/31A61K39/464499A61K39/464835
Inventor T·凯尔佩斯R·V·米格尔
Owner OHIO STATE INNOVATION FOUND
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