Ibritumomab tiuxetan (pronounced ), sold under the trade name Zevalin, 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 antibodie ...

radioimmunotherapy treatment for

non-Hodgkin's 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 tire ...

. The drug uses the monoclonal mouse

IgG1 Immunoglobulin G (IgG) 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 ant ...

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 ...

ibritumomab in conjunction with the chelator tiuxetan, to which a radioactive isotope (either

yttrium-90 Yttrium-90 () is a radioactive isotope of yttrium. Yttrium-90 has found a wide range of uses in radiation therapy to treat some forms of cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the ...

indium-111 Indium-111 (111In) is a radioactive isotope of indium (In). It decays by electron capture to stable cadmium-111 with a half-life of 2.8 days. Indium-111 chloride (111InCl) solution is produced by proton irradiation of a cadmium target (112Cd(p,2n ...

) is added. Tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

group.

Medical use

Ibritumomab tiuxetan is used to treat relapsed or refractory, low grade or transformed

B cell B cells, also known as B lymphocytes, are a type 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 or inserted into the plasm ...

(NHL), a

lymphoproliferative disorder Lymphoproliferative disorders (LPDs) refer to a specific class of diagnoses, comprising a group of several conditions, in which lymphocytes are produced in excessive quantities. These disorders primarily present in patients who have a compromised ...

, and previously untreated follicular NHL in adults who achieve a partial or complete response to first-line

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

. The treatment starts with an infusion of

rituximab 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 children and ad ...

. This may be followed by an administration of

labeled ibritumomab tiuxetan (¹¹¹In replaces the ⁹⁰Y component) to allow the distribution of the medication to be imaged on 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 ...

, before the actual therapy is administered.

Mechanism of action

The antibody binds to the

CD20 B-lymphocyte antigen CD20 or CD20 is B lymphocyte cell-surface molecule. It is a 33-37 kDa non-glycosylated protein. CD20 is expressed on the surface of B-cells from the pre-B phase, the expression is lost in terminally differentiated plasm ...

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. ...

found on the surface of normal and malignant

s (but not B cell precursors), allowing radiation from the attached

isotope Isotopes are distinct nuclear species (or ''nuclides'') of the same chemical element. They have the same atomic number (number of protons in their Atomic nucleus, nuclei) and position in the periodic table (and hence belong to the same chemica ...

(mostly

beta emission In nuclear physics, beta decay (β-decay) is a type of radioactive decay in which an atomic nucleus emits a beta particle (fast energetic electron or positron), transforming into an isobar of that nuclide. For example, beta decay of a neutron t ...

) to kill it and some nearby cells. In addition, the antibody itself may trigger cell death via

antibody-dependent cell-mediated cytotoxicity Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of Cell-mediated immunity, cell-mediated immune defense whereby an effector cell of the immune system kills a target ...

(ADCC), complement-dependent cytotoxicity (CDC), and

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

. Together, these actions eliminate B cells from the body, allowing a new population of healthy B cells to develop from

lymphoid The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...

History

Developed by IDEC Pharmaceuticals, now part of

Biogen Idec Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, United States specializing in the discovery, development, and delivery of the treatment of neurological diseases to patients worldwide. Biogen ope ...

, ibritumomab tiuxetan was the first radioimmunotherapy drug approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) in 2002 to treat cancer. It was approved for the treatment of people with relapsed or refractory, low‑grade or follicular B‑cell non‑Hodgkin's lymphoma (NHL), including people with rituximab refractory follicular NHL. It was given marketing authorization by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

in 2004 for the treatment of adults with rituximab relapsed or

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 ...

CD20+ follicular B-cell non-Hodgkin's lymphoma but. The authorization lapsed in July 2024, after it wasn't marketed for more than three consecutive years. In September 2009, ibritumomab tiuxetan received approval from the FDA for an expanded label to include previously untreated people with a chemotherapy response.

Society and culture

Economics

Ibritumomab tiuxetan is under patent protection and not available in generic form. When approved, it was the most expensive medication available given in a single dose, costing over (€30,000) for the average dose. Compared with other monoclonal antibody treatments (many of which are well over $40,000 for a course of therapy), it may be considered cost effective.

References

{{Authority control Monoclonal antibodies for tumors Antibody-drug conjugates Yttrium compounds Indium compounds Radiopharmaceuticals