An anti-CD22

immunotoxin An immunotoxin is an artificial protein consisting 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 c ...

is a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

(targeting

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 ...

) linked to a

cytotoxic agent 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 ...

. They are being studied in the treatment of some types of

B-cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

. They bind to CD22, a receptor

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

on the surface of normal B cells and B-cell

tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

, and, upon internalization, kill the cells.

Therapeutic immunotoxins that use Pseudomonas exotoxin

As of August 2009, several anti-CD22 immunotoxins are undergoing clinical trials.

CAT-3888 and CAT-8015

CAT-3888 (or BL22) is an anti-CD22 immunotoxin and completed a Phase I clinical (human) trial for the treatment of

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 ...

at the

NIH The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

in the U.S. Technically, CAT-3888 is an anti-CD22 immunotoxin fusion protein between a murine anti-CD22 disulfide-linked Fv (dsFv)

antibody fragment An antibody fragment can be: *a fragment antigen-binding The fragment antigen-binding region (Fab region) 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 lig ...

and an edited copy of bacterial Pseudomonas exotoxin PE38. The toxin is activated intracellularly, by the low pH of the

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...

into which the entire protein was internalized via the CD22 receptor. The toxin kills the targeted cell through

ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...

inactivation. CAT-3888 was initially designed and produced at the U.S.

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

, one of the agencies which make up the

. Early development of BL22 was funded by California biotech

Genencor Genencor is a biotechnology company based in Palo Alto, CA and a subsidiary of IFF. Genencor is a producer of Industrial enzymes and low-priced bulk protein. The name Genencor originates with Genencor, Inc., the original joint venture between Gen ...

. In 2001 results were reported of remissions in a phase I trial for

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

. CAT-3888 was succeeded by

moxetumomab pasudotox 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, includin ...

(CAT-8015, HA22), an anti-CD22 immunotoxin comprising a modified

Pseudomonas exotoxin The Pseudomonas exotoxin (or exotoxin A) is an exotoxin produced by ''Pseudomonas aeruginosa''. ''Vibrio cholerae'' produces a similar protein called the Cholix toxin (). It inhibits elongation factor-2. It does so by ADP-ribosylation of EF ...

and an anti-

antibody fragment.http://www.cambridgeantibody.com/__data/assets/pdf_file/10857/CAT-3888,_CAT-8015_and_CAT-5001_Nov06.pdf CAT URL Redirects to Medimmune home page Like CAT-3888, CAT-8015 changes three amino acids in the antibody fragment to increase the binding affinity for the target molecule. Both of these proteins are designed to bind to the same part of the CD22 receptor on the surface of B cells. Research is being carried on directly by Dr. Robert J. Kreitman at the National Cancer Institute. The patent holder is MedImmune, a subsidiary of AstraZeneca. MedImmune discontinued development of CAT-3888 in 2008 and continues to develop CAT-8015. Early Phase I results find that CAT-8015 exhibits a greater affinity for CD22 than CAT-3888. It may be useful against any B cell

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

, and indeed is currently in a Phase I clinical trial, also at NIH, in patients with non-Hodgkin's lymphoma and chronic lymphocytic leukemia (CLL).

Cambridge Antibody Technology Cambridge Antibody Technology (officially Cambridge Antibody Technology Group Plc, informally CAT) was a biotechnology company headquartered in Cambridge, England, United Kingdom. Its core focus was on antibody therapeutics, primarily using Ph ...

acquired CAT-3888 and CAT-8015 in 2005 from

, a subsidiary of

Danisco Danisco A/S is a Danish bio-based company with activities in food production, enzymes and other bioproducts as well as a wide variety of pharmaceutical grade excipients. It was formed in 1989 from the largest Danish industrial merger ever of th ...

(where they were known as GCR-3888 and GCR-8015). CAT was then purchased in 2007 by British pharmaceutical company

AstraZeneca AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includin ...

for $15.2 billion. AstraZeneca consolidated its biologics portfolio in MedImmune and Cambridge Antibody Technology which was rebranded to create a dedicated biologics division known as 'MedImmune'.AstraZeneca Presents its Global Biologics Organisation, MedImmune, at 2007 Analyst and Investor R&D Day
/ref>

CAT-5001

CAT-5001 (formerly SS1P) is a

that targets mesothelin, which is a cell surface

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

present on normal mesothelial cells that is overexpressed in numerous cancers including

pleural The pleural cavity, pleural space, or interpleural space is the potential space between the pleurae of the pleural sac that surrounds each lung. A small amount of serous pleural fluid is maintained in the pleural cavity to enable lubrication bet ...

and peritoneal mesothelioma,

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...

and

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...

acquired CAT-5001 from Enzon Pharmaceuticals in May 2006.

References

External links

Anti-CD22 immunotoxin
entry in the public domain NCI Dictionary of Cancer Terms {{DEFAULTSORT:Anti-Cd22 Immunotoxin Drugs acting on the blood and blood forming organs Orphan drugs Experimental cancer drugs