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Agents and methods

A substance, CD30 technology, applied in biochemical equipment and methods, chemical equipment and methods, microorganisms, etc., can solve the elusive problems of clinical success

Inactive Publication Date: 2015-07-29
THE UNIV OF BIRMINGHAM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, only a handful of ADCs are currently in late stages of clinical development, and clinical success for these has proven elusive

Method used

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  • Agents and methods

Examples

Experimental program
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Effect test

Embodiment 1

[0223]Example 1: Stimulation of T cells by antibody peptide epitope conjugates (APEC)

[0224] The inventors have shown that by targeting T cell antigens to specific cell surface targets, T cell antigens can be internalized and presented on the surface of cells such that T cell responses are initiated.

[0225] figure 2 A demonstrates T cell recognition of target cells labeled with substances. Anti-CD70 antibodies were conjugated with peptide (PDDYSNTHSTRYV) or without peptide (DMSO) and used to label target cells. Cells labeled with antibodies without peptide were not recognized by T cells, as evidenced by the absence of IFN-γ in the culture supernatant after overnight incubation of target cells and T cells. Cells labeled with antibodies conjugated to immunogenic peptides were strongly recognized by T cells due to the presence of IFN-γ in the culture supernatant. These results indicate that the peptide has been released from the antibody and presented on the cell surface ...

Embodiment 2

[0236] Example 2: Standard Operating Procedure for Chemical Conjugation of Cysteinylated Peptides to Antibodies

[0237] 1. Dissolve cysteinated peptides in DMSO to a final concentration of 10 mg / ml.

[0238] 2. Weigh 1 mg of sulfosuccinimide 4-[N-maleimidomethyl]cyclohexane-1-carboxylate (sulfo-SMCC) and dissolve it in 200 μl of phosphate-buffered saline (PBS )middle.

[0239] a. Other heterobifunctional crosslinkers can be used instead of sulfo-SMCC, such as sulfosuccinimide-6-(3'-[2-pyridyldithio]-propionamido)hexanoate (sulfo base-LC-SPDP) and N-[β-maleimidopropionic acid] hydrazide, trifluoroacetate (BMPH) and others.

[0240] 3. Add 50 μl of antibody (10 mg / ml, 500 μg antibody) to the dissolved sulfo-SMCC and incubate at room temperature for 30 minutes.

[0241] 4. The ZebaSpin desalting column (7 kDa molecular weight) (Thermo Fisher) was first washed by centrifuging the column at 1,500 g for 1 minute to remove ethanol (storage buffer).

[0242] 5. Add 300 μl of PBS ...

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Abstract

The invention provides an agent comprising: (i) a T cell antigen, and (ii) a binding partner for any of CD22, CD23, CD30, CD74, CD70, CD43, CD44, CD47, CD54, CD58, CD62L, CD95, HLA-DR, CD59, CD55, wherein, following binding of the agent to a cell that expresses any of CD22, CD23, CD30, CD74, CD70, CD43, CD44, CD47, CD54, CD58, CD62L, CD95, HLA-DR, CD59, CD55, the agent is internalised and the T cell antigen is presented on the surface of the cell in a form that can be recognised by a T cell.

Description

technical field [0001] The present invention relates to immunotherapeutic agents. In particular, it relates to substances which can be used in the prophylaxis or treatment of disorders characterized by the presence of unwanted cells, such as cells causing tumors or other diseases. Background technique [0002] Immunotherapeutic strategies for targeting malignant diseases are an active area of ​​translational clinical research and have been underway for decades. Current models require that cancers represent functional or constitutional immune deficiencies that can be treated with immunotherapeutic manipulation of the host. These efforts can be broadly divided into two groups. The first group enhanced or supported endogenous anti-tumor immunity through methods such as vaccination, cytokine support (IL-2, IFNγ), or reducing the immunosuppressive environment (ipilimumab), while the second Groups seek to repair absolute deficiencies with functional immune response components (...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K47/00C07K19/00
CPCC07K16/2875A61K39/39558A61K47/48561C07K14/005A61K47/48523A61K47/48415A61K47/6811A61K47/6839A61K47/6849A61K47/6851A61P37/04A61K39/245A61K45/06A61K2039/505A61K2039/572C07K16/30C12N7/00
Inventor 马克·科博尔德大卫·米勒德
Owner THE UNIV OF BIRMINGHAM
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