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Potentiation of the immune response

a technology of immune response and potentiation, applied in the field of viral infection treatment, can solve problems such as t-cell death, and achieve the effect of minimal side effects and potent stimulators of t-cell activity

Inactive Publication Date: 2005-01-13
HUBER BRIGITTE T +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The patent describes a method for stimulating the immune system, particularly in HIV-infected individuals, using low concentrations of inhibitors that target a specific enzyme in T-cells. These inhibitors can either inhibit or enhance the activity of the enzyme, depending on the concentration used. The invention has been found to have several advantages, including the ability to stimulate T-cells without causing toxic effects and the ability to enhance the immune response to vaccination. The invention can also be used as an adjuvant to enhance the immunization of HIV-infected individuals with peptides or other viral antigens."

Problems solved by technology

We believe that this blocking of activation, involving this cytoplasmic activity, prevents differentiation of T-cells of HIV-infected individuals into effector cells, eventually leading to T-cell death.

Method used

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  • Potentiation of the immune response
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  • Potentiation of the immune response

Examples

Experimental program
Comparison scheme
Effect test

example 1

Peripheral blood mononuclear cells (PBMC) were obtained by standard methods from HIV-infected individuals, and from uninfected individuals. Varying dosages of KBP or VBP were contacted with the PBMC in vitro, and stimulation of proliferation was measured by incorporation of 3H thymidine (cpm). The results of these experiments are shown in FIG. 1: very low doses of the Val-boroPro and Lys-boroPro stimulated proliferation of PBMC from HIV-infected patients, but not PBMC from uninfected patients.

As shown in FIG. 1, at no concentration of the boroPro enzyme inhibitor did it affect the PBMC from uninfected individuals. The inhibitor, at moderate concentrations, also did not cause proliferation of PBMC from HIV-infected individuals. but it did cause marked proliferation at very low concentrations (10−9 and 10−10). These results are consistent with our hypothesis, discussed above, that at low concentrations, these enzyme inhibitors exhibit a paradoxical effect: rather than inhibiting th...

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Abstract

A method for stimulating proliferation of T-cells containing cytoplasmic post-prolyl dipeptidase activity; the method, in one aspect, involves contacting the T-cells with an organic compound at a concentration below 10−8M, wherein the compound is characterized in that: (a) it is capable of crossing the membrane of T-cells to enter the cytoplasm, (b) it binds to the dipeptidase activity at a concentration of below 10−8M, and thus (c) stimulates proliferation of the T-cells at that concentration.

Description

BACKGROUND OF THE INVENTION This invention relates to treatment of viral infections using organic compounds which interact with T-cell enzymes. One of the classic markers of full-blown AIDS resulting from long-term infection with HIV-1 is a severe depletion of CD4+ T-cells, which are a key component of the immune system. Attempts have been made to increase the CD4+ counts of AIDS patients, and some of these efforts, notably treatment with protease inhibitors, have met with considerable success. Other approaches, e.g., stimulation of the immune response by vaccination with viral peptides, have been less successful. The reasons for CD4+ depletion in AIDS, and resistance of CD4+ cells to stimulation by some therapies are not fully understood. SUMMARY OF THE INVENTION We have discovered that the activation state of human T-cells can be affected by compounds which interact with a cytoplasmic post-prolyl dipeptidase activity which has similarities to, but is distinct from, the membrane...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/55A61K45/00A61K39/39A61P31/18A61P37/04C07K14/155C07K14/73
CPCA61K38/55A61K39/39G01N2333/96433A61K2039/55516G01N2333/16A61K2039/55511A61P31/18A61P37/04A61P43/00Y02A50/30
Inventor HUBER, BRIGITTE T.SCHMITZ, TRACYUNDERWOOD, ROBERT
Owner HUBER BRIGITTE T