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

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

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

endocytosis Endocytosis is a cellular process in which Chemical substance, 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 (biology and chem ...

, 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 proteins are usually made of a modified

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

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 pathogenic bacteria, though there is a pore-forming AB toxin found in the eggs of a snail. They can be classified as Type III toxins because they interfere with internal ce ...

, a

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

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 fo ...

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, moiety, foreign particulate matter, or an allergen, such as pollen, 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 (or refractory material) is a material that is resistant to decomposition by heat or chemical attack and that retains its strength and rigidity at high temperatures. They are inorganic, non-metallic compound ...

hairy cell leukemia Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. The incidence of hairy cell leukemia (HCL) is 0.28-0.30 cases per 100,000 people in Europe and the United States and the pre ...

. 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 tha ...

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, a slightly modified version. A recent Phase I study of Resimmune found an 89% response rate in a subgroup of nine patients with cutaneous T cell lymphoma.
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