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Methods and molecules for modulating an immune response

a technology of immune response and modulation, applied in the direction of antibody medical ingredients, drug compositions, peptides, etc., can solve the problems of asthma symptoms, achieve the effects of reducing the risk of allergic asthma

Inactive Publication Date: 2010-10-14
MAYO FOUND FOR MEDICAL EDUCATION & RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent is about a method for treating allergic asthma in mammals by using a B7-DC cross-linking molecule, such as an antibody, to modulate the immune response. The treatment can be given before or after exposure to allergens, and it can protect against airway hyperreactivity and inflammation. The method can also be used to inhibit the development of allergic asthma or a Th2 response. The patent also describes a recombinant polypeptide that can cross-link B7-DC molecules and modulate dendritic cell function. Overall, the patent provides methods for preventing and treating allergic asthma and related conditions.

Problems solved by technology

Through a complex reaction, these allergens then cause the passages in the airways of the lungs to become inflamed and swollen, resulting in asthma symptoms.

Method used

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  • Methods and molecules for modulating an immune response
  • Methods and molecules for modulating an immune response
  • Methods and molecules for modulating an immune response

Examples

Experimental program
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Effect test

example 1

Materials and Methods for Isolating and Characterizing SHIgM12

[0093]Isolation of human antibodies—Human serum samples were obtained from the dysproteinemia clinic, and those exhibiting an Ig clonal peak of greater than 20 mg / ml were chosen for further evaluation. The selected samples were from 50 patients with a wide variety of conditions characterized by a monoclonal IgM spike, including Waldenstrom's macroglobulinemia, lymphoma, and monoclonal gammopathy of undetermined significance. Sera were dialyzed against water, and precipitates were collected by centrifugation at 14,000 rpm for 30 minutes and dissolved in phosphate buffered saline (PBS). The samples were centrifuged and chromatographed on a Superose-6 column (Amersham Pharmacia, Piscataway, N.J.). IgM fractions were pooled and analyzed by SDS-PAGE, and protein concentrations were determined by reading absorbance at 280 nm. IgM solutions were sterile filtered and cryopreserved. The antibody sHIgM12 was identified based on its...

example 2

A Monoclonal Human IgM Antibody Binds Mouse DC

[0117]DC were obtained in culture following incubation of mouse bone marrow cells in media supplemented with GM-CSF and IL-4. Cells from seven day cultures were incubated with purified antibodies isolated from human sera, and stained with fluoresceinated goat anti-human antibody as well as antibodies specific for cell surface molecules typically expressed on DC. As shown in FIG. 1, the human antibody sHIgM12 bound cells in the cultures that expressed high levels of CD11c, class II, and CD86. Polyclonal human IgM, as well as the other tested monoclonal antibodies from patients with gammopathies or from EBV-transformed cell lines did not appreciably bind the DC populations.

[0118]To determine when the cell surface determinant recognized by the sHIgM12 antibody first appears during the in vitro development of DC, cultured cells were analyzed by flow cytometry at various times during the culture procedure. The determinant first appeared on da...

example 3

The SHIgM12 Antibody Potentiates Dendritic Antigen-Presenting Function

[0120]To determine whether binding of sHIgM12 to the surface of DC influences the pattern of expressed cell surface molecules, day 7 DC cultures were supplemented with 10 μg / ml antibody, incubated overnight, and analyzed by flow cytometry. No changes in cell surface markers specific to sHIgM12 treatment were observed as compared to cultures treated with human polyclonal IgM antibodies or other monoclonal human IgM antibodies.

[0121]The antigen-presenting functions of the DC were assessed in vitro. Antibody-treated DC were pulsed with peptide antigen and used to stimulate naïve antigen-specific T cells freshly isolated from OT-1 and DO-11 transgenic mice. T cell activation was measured by incorporation of 3H-thymidine as described in Example 1. DC that were pulsed with a class I-binding peptide (Ser-Ile-Ile-Asn-Phe-Glu-Lys-Leu; SEQ ID NO:1) and incubated with polyclonal HIgM control antibody were able to activate na...

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Abstract

A molecule capable of potentiating immune responses and modifying existing states of immune responsiveness is described. Also described are compositions containing the molecule, as well as methods for using the molecule and the compositions to enhance immune responses, to enhance DC function, to modify an existing state of immune responsiveness, to immunize individuals, or to treat or inhibit conditions such as allergic asthma.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 10 / 881,661, filed on Jun. 30, 2004.TECHNICAL FIELD[0002]This invention relates to methods for treating or decreasing development of allergic asthma, and more particularly to using a B7-DC cross-linking antibody to treat or inhibit development of allergic asthma. The invention also relates to methods for modulating an existing state of immune responsiveness.BACKGROUND[0003]Decavalent IgM antibodies display measurable binding avidity to antigens, even though binding affinity may be low. The multivalent structure of pentameric IgM provides the potential for cross-linking cell surface targets, endowing the soluble antibodies with biological potential not normally associated with immune function. Dendritic cells (DC) are efficient antigen-presenting cells (APC). These cells express class I and class II major histocompatibility complex (MHC) peptide-presenting molecules on their ce...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61P11/06
CPCA61K2039/505C07K2317/22C07K16/2827A61P11/06
Inventor RADHAKRISHNAN, SURESHPEASE, LARRY R.KITA, HIROHITOIIJIMA, KOJI
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
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