Chimeric Anti-ricin antibody

Abstract

A chimeric monoclonal antibody targeted to ricin is presented. The light chain and heavy chain constant regions are respectively made up of the light chain and heavy chain constant regions of human immunoglobulin, and the light chain and heavy chain variable regions respectively include the light chain and heavy chain variable regions of macaque immunoglobulin. The antibody does not substantially induce any immune response against chimeric antibodies.

Description

FIELD OF THE INVENTION[0001]This invention concerns a chimeric antibody directed against Ricin.BACKGROUND OF THE INVENTION[0002]Ricin is a toxalbumin produced by a shrub belonging to the Euphorbiaceae family, the Castor Oil Plant (Ricinus communis). Ricin is a highly toxic glycoprotein with a molecular weight of 66 kDa formed by two polypeptide chains A and B connected together by a disulphide bridge. Chain B allows the toxin to attach itself to the cell wall while Chain B, which is responsible for its toxic properties, is capable of inhibiting protein synthesis by inhibiting 28S ribosomal RNA, causing cell death. It is present in the castor oil seed in concentrations of between 1% and 10%. It may be extracted from incompletely purified castor oil.[0003]As a toxin, ricin is extremely toxic. However, its toxicity varies according to the means by which it penetrates the organism.[0004]When ricin is absorbed through digestion, it is largely destroyed by proteolytic digestive enzymes bu...

AI Technical Summary

Benefits of technology

[0167]The measure of apoptosis, or programmed cell death, is made by techniques routinely employed by experts in this field which involve the evaluation of at least one of the stages characteristic of apoptosis: modification of the plasma membrane, modification of the proteins from the Caspase family, modification of the factors of transactions and fragmentation of DNA. Among the cells or cell lines obtained by cloning, the advantage of the invention is that the cells conserved are only those which produce a significant quantity of monoclonal antibody, and notably those which produce at least 20 μg / ml of monoclonal antibody. The measure of the quantity of antibody is easily achievable by the experts, using simple protein dosage techniques.

[0168]Another embodiment of the invention concerns a cell or a cell line obtained by the cloning of the aforementioned cell, notably characterised by the fact that:

[0171]it secretes at least 14 μg / ml of monoclonal antibody previously defined.

[0172]The notion of cellular stability implies that the cells from the cloning of cells cloned from cells containing at least one vector permitting the expression of a monoclonal antibody in accordance with the invention are capable during the different divisions of conserving their properties of resistance to antibiotics and of producing the monoclonal antibodies.

[0173]A further aspect of the invention concerns the pharmaceutical composition, in particular vaccinal, comprising at least

[0177]one fragment of the said monoclonal antibody defined above,combined with a vehicle pharmaceutically acceptable.

Problems solved by technology

As a toxin, ricin is extremely toxic.

However, its toxicity varies according to the means by which it penetrates the organism.

Absorption via inhalation causes weakness, fever, dizziness, dyspnoea, coughing, pulmonary oedemas and pain in the limbs.

After an apparent improvement, infection may have a fatal outcome.

However, no ricin-specific therapy is currently available.

However, although this first-generation chimeric antibody is ricin-specific, it is capable of generating a Human Anti-Chimeric Antibody (HACA) immune response and of inducing low patient tolerance.

However, such fragments are small in size, have a very short half-life, are rapidly eliminated by the kidneys and are incapable of providing long-term protection.

Furthermore, given the lack of a constant region, these fragments are relatively ineffective at stimulating the immune system (recruitment of immune effectors).

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