An immunotoxin is an artificial protein consisting of a targeting portion linked to a

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

. When the protein binds to that cell, it is taken in through

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...

, and the toxin kills the cell. They are used for the treatment of some kinds of cancer and a few viral infections.

Design

These

chimeric protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this ''fusion gene'' r ...

s are usually made of a modified

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

or antibody fragment, attached to a fragment of a

. The targeting portion is composed of the Fab portion of an antibody that targets a specific cell type. The toxin is usually an

AB toxin The AB toxins are two-component protein complexes secreted by a number of pathogenicity, pathogenic bacteria, though there is a pore-forming AB toxin found the eggs of a snail. They can be classified as Exotoxin#Type III: intracellular, Type III t ...

, a

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

protein derived from a bacterial or plant protein, from which the natural binding domain has been removed so that the Fv directs the toxin to the antigen on the target cell. Sometimes recombinant fusion proteins containing a toxin and a growth factor are also referred to as recombinant immunotoxins, although they do not contain an antibody fragment. A more specific name for this latter kind of protein is recombinant fusion toxin.

Production

They were originally produced by attaching the antibody to the toxin using a chemical linker. They are now made using

recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...

techniques, are produced in bacteria like ''E. coli'' called recombinant immunotoxins.

Function

The antibody (or other targeting moiety) binds to an

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

on the target cell and the toxin then enters and kills the cell.

Clinical application

The best clinical success has been achieved in treating patients with

refractory In materials science, a refractory material or refractory is a material that is resistant to decomposition by heat, pressure, or chemical attack, and retains strength and form at high temperatures. Refractories are polycrystalline, polyphase, ...

hairy cell leukemia Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a subtype of chronic lymphocytic leukemia (CLL). Hairy cell leukemia makes up about 2% of all le ...

. These patients were treated with the recombinant immunotoxin which targets the

CD22 CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that ...

cell surface receptor on these leukemic cells. In two uncontrolled clinical studies, about half of participants achieved a complete response after BL22 treatment. This therapeutic has been superseded by

HA22 Moxetumomab pasudotox, sold under the brand name Lumoxiti, is an anti-CD22 immunotoxin medication for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including ...

, a slightly modified version. A recent Phase I study of

Resimmune Resimmune or A-dmDT390-bisFv(UCHT1) is an experimental drug — an anti-T cell immunotoxin — that is being investigated for treatment of blood cancers such as cutaneous T cell lymphoma (CTCL). It was developed by Doctors Neville, Woo, ...

found an 89% response rate in a subgroup of nine patients with

cutaneous T cell lymphoma Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin lymphomas (which are generally B-cell-related), CTCL is caused by a mutation of T cells. The cancerous T ...

.
Angimmune: Clinical Trials: Identification of a Cutaneous T-Cell Lymphoma (CTCL) Subgroup Experiencing a High Treatment Response Rate: Paragraph 1 This subgroup was Stage IB-IIB with mSWAT scores of less than 50. The complete response rate was 50% (two of which are over 72 months duration and could represent cures).

References

External links