Method and device for modulating the immune response

A technology of immune response and immune cells, which is applied in the field of regulating the immune response to antigens, and can solve problems such as treatment technology and material difficulties

Inactive Publication Date: 2001-06-13
APPLIED VACCINE TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Despite significant research being done to address these shortcomings in the availabil

Method used

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  • Method and device for modulating the immune response
  • Method and device for modulating the immune response
  • Method and device for modulating the immune response

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] An example of making the device of the present invention is to take a piece of silicone tubing with an inner diameter of 0.15 cm, an outer diameter of 0.2 cm, and a length of 2.5 cm, and fill it with a length of hydroxylated polyvinyl acetate sponge of 2.5 cm. The device was submerged in a container containing phosphate buffered saline and autoclaved. Anesthetize female BALB / c mice (6-8 weeks old) with tribromoethanol. The device was inserted through a 0.5 cm incision in the dorsal midline on day 1. At 2 days post-implantation, some animals were introduced into the device with 50 μl of 1 mg / ml influenza antigen (FLUSHIELD® influenza virus vaccine, trivalent, types A & B; from Henry Schein®, Melville NY) by piercing the device with an injection needle. The skin near the implanted device is penetrated, and the needle is then guided into one end of the device by feel.

[0074] Fluid was aspirated from the implanted devices of 5 animals each at 2, 4, 7 and 9 days post-imp...

Embodiment 2

[0076] This experiment utilizes BALB / c mice to detect the number and phenotype of cells present in the device. During the 4 days following device implantation as described in Example 1, cells were aspirated from the devices of 5 animals each, pooled, washed, and distributed into several test tubes. Add fluorescein isothiocyanate or phycoerythrin-labeled monoclonal cells specific for the following markers (CD14, CD45 / B220, CD11b, CD40, CD11c, CD80, CD86, CD62P, CD62E, CD3, and I-Ad). Antibodies were cloned, incubated at 4°C for 30-45 minutes, then cells were washed and the geometric mean fluorescence was measured using a flow cytometer. For comparison, the same panel of specific antibodies was also used to measure the fluorescence of peripheral blood lymphocytes from syngeneic untreated mice and the results obtained for each antibody were expressed as the increase in fluorescence of cells from the device relative to peripheral blood lymphocytes percentage.

[0077] figure 2 ...

Embodiment 3

[0079] The change in cell population in the device as described in Example 1 over time was calculated by harvesting cells from the device at 3, 7 and 10 days after implantation. In the first experiment, the device did not contain any antigens. The cells aspirated from the implanted devices of 5 mice at each time point were pooled and tested for CD3, CD8, CD80, CD44, CD11c, CD45R / B220 and CD14 markers in the same manner as described in Example 2. The density of cells was expressed as the percentage increase relative to the peripheral blood lymphocytes of untreated mice.

[0080] image 3 The calculated density of cells of each phenotype at 3, 7 and 10 days post-implantation is given. For all markers, enrichment of each cell type in the device was evident on days 3 and 7, while by day 10 the cell population had migrated out of the device.

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Abstract

The present invention provides methods and devices for inducing, stimulating, blocking and reducing the immune response of a mammal to an antigen, using an implantable device which exposes the antigen in a controlled fashion to cells of the immune system. The device comprises a porous matrix contained within a perforated, impermeable container. By manipulating the bioavailability of antigen within the device, and the timing of introduction of antigen into the device relative to the time of implantation of the device within the mammal, a robust and long-term response can be induced against an antigen, or an existing or potential immune response can be down regulated or blocked. The methods and devices can be used for therapeutic vaccination, and in non-exposed mammals for prophylactic vaccination. Immunity can be cellular, humoral, or mucosal. Suppression of the immune response is useful for the treatment or prophylaxis of such conditions as allergies, autoimmune disease, and in tolerizing mammals to suppress an immune response to transplant antigens. The device can also be used for harvesting immune cells for later reintroduction into the mammal, and for preparing immune serum and hybridomas.

Description

field of invention [0001] The present invention generally relates to a method of modulating an immune response to an antigen in a mammal using an implantable device that exposes the antigen to cells of the immune system in a controlled manner. By establishing an artificial environment that mimics the composition and function of lymph nodes and regulating the bioavailability of antigens in the device, a strong response against a certain antigen can be induced, or an existing immune response can be down-regulated. Background of the invention [0002] The induction of an immune response to an antigen, as well as the strength of that response, depend on complex interactions between the antigen, various immune cells, and co-stimulatory molecules including cytokines and chemokines. The timing and extent of immune cell exposure to antigenic and co-stimulatory environments can further modulate the immune response. These different types of cells and cofactors in the ...

Claims

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Application Information

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IPC IPC(8): C12N15/09A61K9/00A61K39/00A61K48/00C07K16/00C07K17/02C12N5/10C12P21/08C12R1/91
CPCA61K9/0024A61P37/00A61P37/04A61K9/00
Inventor A·切拉米C·切拉米C·格尔贝尔D·达夫
Owner APPLIED VACCINE TECH CORP
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