Immunotoxin
Encyclopedia
An immunotoxin is a human-made protein that consists of a targeting portion linked to a toxin
. When the protein binds to that cell, it is taken in through endocytosis
, and the toxin kills the cell. They are used for the treatment of some kinds of cancer and a few viral infections.
or antibody fragment, attached to a fragment of a toxin
. The targeting portion is composed of the Fv portion of an antibody
that targets a specific cell type. The toxin is usually a cytotoxic
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 though they do not contain an antibody fragment. A more specific name for this latter kind of protein is recombinant fusion toxin.
techniques, are produced in bacteria like E. coli and are called recombinant immunotoxins.
on the target cell and the toxin then enters and kills the cell.
. These patients were treated with the recombinant immunotoxin, BL22, which targets the CD22
cell surface receptor, which is highly expressed 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 This therapeutic has been superseded by HA22, a slightly modified version.
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
. When the protein binds to that cell, it is taken in through endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
, 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 antibodyAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
or antibody fragment, attached to a fragment of a toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
. The targeting portion is composed of the Fv portion of an antibody
Fragment antigen binding
The fragment antigen-binding is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. These domains shape the paratope — the antigen-binding site — at the amino terminal end of the monomer...
that targets a specific cell type. The toxin is usually a cytotoxic
Cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...
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 though 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 DNARecombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
techniques, are produced in bacteria like E. coli and are called recombinant immunotoxins.
Function
The antibody (or other targeting moiety) binds to an antigenAntigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
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 hairy cell leukemiaHairy cell leukemia
Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia...
. These patients were treated with the recombinant immunotoxin, BL22, which targets the CD22
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...
cell surface receptor, which is highly expressed 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.
See also
- Denileukin diftitoxDenileukin diftitoxDenileukin diftitox is an antineoplastic agent, an engineered protein combining Interleukin-2 and Diphtheria toxin. This can bind to Interleukin-2 receptors and introduce the diphtheria toxin into cells that express those receptors, killing the cells...
, an immunotoxin used to treat T cell leukemias - Anti-CD22 immunotoxins, being tested in hairy cell leukemia
- Antibody-drug conjugateAntibody-drug conjugateAntibody-drug conjugates are a new type of targeted therapy, used for example for cancer. They consist of an antibody linked to a payload drug . Hence, they are a type of immunoconjugate and often an immunotoxin.The antibody causes the ADC to bind to the target cancer cells...
s, most, if not all, are immunotoxins but use whole antibodies and non-protein drugs - Immunopharmacology and ImmunotoxicologyImmunopharmacology and ImmunotoxicologyImmunopharmacology and Immunotoxicology is a quarterly peer-reviewed medical journal that covers preclinical and clinical studies on the regulatory effects of various agents on immunocompetent cells, as well as the immunotoxicity exerted by xenobiotics and drugs. Hence, the journal encompasses a...
(medical journal)