Method for treatment of malignant and infectious chronic diseases

a chronic disease and infectious technology, applied in the field of treatment, can solve the problems of poor success of combining specific active immunotherapy with chemotherapy, inability to induce an effective tumoral regression in humans, and inability to achieve effective tumoral regression. , to achieve the effect of increasing the autoimmune respons

Inactive Publication Date: 2006-11-09
CENT DE INMUNOLOGIA MOLECULAR CENT DE INMUNOLO
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In spite of the several evaluations of this approach, most of the intents of inducing an effective tumoral regression in humans has not been successful.
The poor induction of a specific immune response in cancer patients has been the main trouble.
Moreover, it has been established that deficiency of T cells or anergy is not the reason for the growth of the antigenic tumor cells.
With little success various candidates have been evaluated as much in experimental protocols as in clinical trials.
Nevertheless this strategy in many cases does not increase substantially the immune response and in other cases it is abolished after the induction.
Nevertheless, combining specific active immunotherapy with chemotherapy has poor success, in this sense, lymphopenia in cancer patients induced by chemotherapy has been reported (Mackall CL.

Method used

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  • Method for treatment of malignant and infectious chronic diseases
  • Method for treatment of malignant and infectious chronic diseases
  • Method for treatment of malignant and infectious chronic diseases

Examples

Experimental program
Comparison scheme
Effect test

example 1

Comparison Between Two Treatment Schemes on the Induction of Antibodies Against Human EGF in Healthy Mice (VIV vs IVV). Immune Modulating with Anti-Mammalian T Cells Antibodies

[0060] The transitory immune modulation with anti-CD4 and anti-CD8 Monoclonal Antibodies increases the antibody response against Epidermal Growth Factor and it depends on the treatment scheme used.

[0061] BALB / c mice were immunized using two combined protocols: According to the scheme, (1) the mice were injected by intravenous route with a dose of 0.5 mg of anti-CD4 or anti-CD8 monoclonal antibodies (MAbs). Five days later mice were immunized by subcutaneous route with 50 μg of human Epidermal Growth Factor (hu-EGF) in Complete Freund Adjuvant, two weeks later, the mice were re-immunized by subcutaneous route with a second dose of 50 μg of hu-EGF in Incomplete Freund Adjuvant (IFA).

[0062] According to the scheme (2), the mice were injected by subcutaneous route with 50 μg of human Epidermal Growth Factor (hu...

example 2

Comparison Between Two Treatment Schemes on the Induction of Antibodies Against Autologous EGF in Healthy Mice (VIV vs IVV). Immune Modulating with Anti-Mammalian T Cells Antibodies

[0063] The transitory immune modulation with anti-CD4 and anti-CD8 monoclonal antibodies increases the antibody response against the autologous Epidermal Growth Factor.

[0064] BALB / c mice were immunized using two protocols combined similar to that described in Example 1 and the IgG antibody response against murine EGF (autologous) was measured. FIG. 2 shows that the immune modulation with both anti-CD4 and anti-CD8 Mabs using the scheme (2) also increases the of IgG antibody response against the murine EGF, the one that was significantly higher than the response exhibited by the mice immunized twice with hu-EGF and treated with saline solution, which were used as control. It is shown the geometric average of the IgG antibody titers for each group at day 47 after the first immunization.

example 3

Tumor Effect on the Induction of an Antibody Response Against Vaccine Antigens

[0065] The immune response against vaccine containing self-antigens diminishes by the presence of tumor in the immunized subjects.

[0066] C57BL / 6 mice were injected by intramuscular route with a vaccine that contains 4 μg of human EGF conjugated to the P64 protein (EGF-p64) in Montanide ISA 51 (100 μl final volume) and two weeks later were re-immunized by intramuscular route with a second dose of said vaccine. A group of these animals was inoculated with the syngeneic tumor 3LL-D122 (200 000 cells / animal) in the right plantar pad 2 days previous to the first immunization.

[0067]FIG. 3 shows that the presence of the syngeneic tumor influences negatively in the induction of the immune response against the vaccinal antigen. The individual titers of IgG+IgM antibodies are shown for each group day 47 after the first immunization.

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Abstract

The present invention relates to methods of treatment useful in chronic diseases, by means of breaking tolerance to self-antigens and increasing autoimmune response against these antigens. More particularly, the present invention relates to methods useful in the treatment of tumors that are growth dependent on the Epidermal Growth Factor. The present invention provides a therapeutic combination that includes the combination of a vaccine against self antigens with a monoclonal antibody against peripheral T cells or a chemotherapeutic drug able to induce a depletion of peripheral T cells. The present invention also provides a method of treatment of chronic diseases in which the rupture of the tolerance to self antigens is essential for the control of the disease, by administering an immune suppressor agent between two cycles of vaccination against a self antigen, for example EGF, for effective treatment for the reduction of tumors whose growth depends on EGF.

Description

CROSS-REFERENCE [0001] This application is a divisional application of Ser. No. 10 / 309,015, filed Dec. 4, 2002, which is incorporated herein by reference in its entirety, and to which application we claim priority under 35 USC § 121, which claims the benefit of foreign application Cuba CU 286 / 2001, filed Dec. 4, 2001, which is incorporated herein by reference in its entirety, and to which application we claim priority under 35 USC § 119(a).BACKGROUND OF THE INVENTION [0002] The cancer immunology is based on the premise of tumor-associated antigens, which are expressed by human tumors and not in normal tissues. An alternative to control the division and proliferation of the malignant cells has been to isolate these antigens and present them so that they are recognized by the immune system as non-self antigens and this way to induce a specific immune response. In spite of the several evaluations of this approach, most of the intents of inducing an effective tumoral regression in human...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K39/02A61K31/337A61K31/66A61K33/243A61K39/00C07K16/22C07K16/28
CPCA61K31/337A61K31/66C07K16/2866C07K16/2815C07K16/2812C07K16/22A61K2039/6068A61K2039/55505A61K2039/505A61K33/24A61K39/0005A61K39/0011A61K39/395A61K2300/00A61K39/001131A61K33/243
Inventor CASIMIRO, JOSE ENRIQUE MONTERORODRIGUEZ, ROLANDO PEREZDAVILA, AGUSTIN BIENVENIDO LAGE
Owner CENT DE INMUNOLOGIA MOLECULAR CENT DE INMUNOLO
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