Tositumomab is a

murine The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families ex ...

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 ...

which targets the

CD20 B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase ( CD45R+, CD117+) and progressively increasing in concentration until maturity. In humans CD20 is encoded by the ''MS4A1'' gene. This gene ...

antigen produced in mammalian cell. It was combined with

iodine-131 Iodine-131 (131I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nu ...

to produce a

radiopharmaceutical Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which ...

for

unsealed source radiotherapy Radionuclide therapy (RNT, also known as unsealed source radiotherapy or molecular radiotherapy) uses radioactive substances called radiopharmaceuticals to treat medical conditions, particularly cancer. These are introduced into the body by vario ...

, Iodine-131 Tositumomab (branded as Bexxar), for the treatment of non-Hodgkins lymphoma. It is classified as a

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...

2a lambda antibody. The drug combination was developed by

Corixa ''Corixa'' is a genus of aquatic bugs in the family Corixidae. The fossil species ''C. elegans'' is from the Rott Formation The Rott Formation is a geologic formation in Germany Germany,, officially the Federal Republic of German ...

which was purchased by GlaxoSmithKline in 2005. It was sold for about $25,000 for one round of treatment. Bexxar competed with Zevalin, until the former's discontinuation in 2014.

Clinical use

A personalized regimen using Bexxar was approved for the treatment of relapsed or

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

rituxan Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric pa ...

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, ...

Non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tirednes ...

in 2003. The radioactive dose was adjusted for each patient in order to maximize the radiation delivered to the tumor and minimize the exposure of other organs. Bexxar combined separate administration of unlabelled and iodine-labelled (i.e.

covalently bonded A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...

to ¹³¹I) tositumomab. A first dose of labelled antibody was given once, and whole-body radiation was measured with a

gamma camera A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...

over seven days. Analysis of that imaging data allowed an optimal dose of labelled antibody to be calculated, which was then administered once a day, for up to seven days. Each time the labelled antibody was administered, it was always preceded by unlabelled (non-radioactive) antibody. Early

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s had shown that total body residence times of radioactivity were longer in people who first received unlabelled antibody, so that a lower dose of labelled antibody was needed to deliver the required total dose of radiation; additionally labelled antibody targeted tumors better in people pre-treated with unlabelled antibody.

Availability

United States

Following a first investigational new drug application in 1989 and

biologics license application A biologics license application (BLA) is defined by the U.S. Food and Drug Administration (FDA) as follows: The biologics license application is a request for permission to introduce, or deliver for introduction, a biologic product into inters ...

in 2000, Bexxar was approved by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

in 2003. Sale of Bexxar was discontinued and marketing approval was withdrawn in February 2014 due to a decline in usage (fewer than 75 patients in 2012). One possible explanation for the lack of demand, despite a claimed 70% response rate, was that

oncologist Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...

s could not sell it directly to patients but had to refer patients to third party specialist centers, however a "muddled clinical trials strategy", supply chain issues, reimbursement problems, and emergence of non-radioactive competitors has also been blamed.

Europe

The European Medicines Agency granted tositumomab and ¹³¹I-tositumomab

orphan drug status An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment o ...

, for the treatment of

follicular lymphoma Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. These cells norma ...

, to

Amersham plc Amersham plc was a manufacturer of radiopharmaceutical products, to be used in diagnostic and therapeutic nuclear medicine procedures. The company became GE Healthcare following a takeover in 2003, which was based at the original site in Amersh ...

in 2003. This was withdrawn in October 2015 at the request of the new owner, GlaxoSmithKline.

References

{{Therapeutic radiopharmaceuticals Monoclonal antibodies GSK plc brands