Tositumomab
Identification
- Summary
Tositumomab is a monoclonal anti-CD20 antibody used to treat B-cell non-Hodgkin's lymphoma via a conjugated radioactive isotope.
- Generic Name
- Tositumomab
- DrugBank Accession Number
- DB00081
- Background
Murine IgG2a lambda monoclonal antibody against CD20 antigen (2 heavy chains of 451 residues, 2 lambda chains of 220 residues). It is produced in an antibiotic-free culture of mammalian cells. It can be covalently linked to Iodine 131 (a radioactive isotope of iodine).
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6416H9874N1688O1987S44
- Protein Average Weight
- 143859.7 Da
- Sequences
>Mouse-Human chimeric Anti-CD20 Heavy Chain 1 QAYLQQSGAELVRPGASVKMSCKASGYTFTSYNMHWVKQTPRQGLEWIGAIYPGNGDTSY NQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYFCARVVYYSNSYWYFDVWGTGTTVTV SGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK
>Mouse-Human chimeric Anti-CD20 Light Chain 1 QIVLSQSPAILSASPGEKVTMTCRASSSVSYMHWYQQKPGSSPKPWIYAPSNLASGVPAR FSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGAGTKLELKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNR
>Mouse-Human chimeric Anti-CD20 Heavy Chain 2 QAYLQQSGAELVRPGASVKMSCKASGYTFTSYNMHWVKQTPRQGLEWIGAIYPGNGDTSY NQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYFCARVVYYSNSYWYFDVWGTGTTVTV SGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK
>Mouse-Human chimeric Anti-CD20 Light Chain 2 QIVLSQSPAILSASPGEKVTMTCRASSSVSYMHWYQQKPGSSPKPWIYAPSNLASGVPAR FSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGAGTKLELKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNR
Download FASTA Format- Synonyms
- Tositumomab
Pharmacology
- Indication
For treatment of non-Hodgkin's lymphoma (CD20 positive, follicular)
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- Pharmacodynamics
Tositumomab binds to the CD20 antigen, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin's lympohomas. The antibody leads to selective killing of B-cells.
- Mechanism of action
Binds to the CD20 antigen which is found on mature B lymphocytes. The antibody binding appears to induce apoptosis, complement-dependent cytotoxicity and cell death through ionizing radiation.
Target Actions Organism AB-lymphocyte antigen CD20 antibodyHumans ULow affinity immunoglobulin gamma Fc region receptor II-b Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Most likely removed by opsonization via the reticuloendothelial system when bound to B lymphocytes, or by human antimurine antibody production
- Route of elimination
Elimination of Iodine-131 occurs by decay and excretion in the urine.
- Half-life
0.8 hours (mammalian reticulocytes, in vitro)
- Clearance
- 68.2 mg/hr [patients with NHL]
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Tositumomab may decrease the excretion rate of Abacavir which could result in a higher serum level. Abatacept The risk or severity of adverse effects can be increased when Tositumomab is combined with Abatacept. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Tositumomab. Aceclofenac Aceclofenac may decrease the excretion rate of Tositumomab which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Tositumomab which could result in a higher serum level. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Tositumomab I-131 K1KT5M40JC Not Available Not applicable - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bexxar Dosimetric Injection 0.61 mCi/1mL Intravenous Glaxosmithkline Inc 2009-07-15 2014-02-13 US Bexxar Therapeutic Injection 5.6 mCi/1mL Intravenous Glaxosmithkline Inc 2009-07-15 2014-02-20 US Bexxar Therapy Kit; Solution 14 mg / mL Intravenous Glaxosmithkline Inc 2006-04-10 2014-07-31 Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Bexxar Tositumomab (14 mg/1mL) + Tositumomab (14 mg/1mL) Kit Intravenous Glaxosmithkline Inc 2009-07-15 2014-11-28 US Bexxar Tositumomab (14 mg/1mL) + Tositumomab (14 mg/1mL) Kit Intravenous Glaxosmithkline Inc 2009-07-15 2014-11-28 US
Categories
- ATC Codes
- V10XA53 — Tositumomab/iodine (131i) tositumomab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antigens, CD20
- Antineoplastic Agents
- Blood Proteins
- CD20-directed Antibody Interactions
- CD20-directed Radiotherapeutic Antibody
- Drugs that are Mainly Renally Excreted
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Iodine (131I) Compounds
- Myelosuppressive Agents
- Proteins
- Radioimmunotherapy
- Radiopharmaceutical Activity
- Serum Globulins
- Therapeutic Radiopharmaceuticals
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 0343IGH41U
- CAS number
- 208921-02-2
References
- General References
- Not Available
- External Links
- UniProt
- P01857
- Genbank
- J00228
- PubChem Substance
- 46506662
- 263010
- ChEMBL
- CHEMBL1201604
- Therapeutic Targets Database
- DAP000384
- PharmGKB
- PA164748364
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Tositumomab
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment B-Cell Lymphoma / Immunoblastic Large Cell Lymphoma / Non-Hodgkin's Lymphoma (NHL) 1 3 Completed Treatment Non-Hodgkin's Lymphoma (NHL) 1 2 Active Not Recruiting Treatment Multiple Myeloma (MM) 1 2 Completed Treatment B-Cell Lymphoma 1 2 Completed Treatment Lymphoid Leukemia in Remission / Stage I Chronic Lymphocytic Leukemia / Stage II Chronic Lymphocytic Leukemia / Stage III B-cell small lymphocytic lymphoma / Stage III Chronic Lymphocytic Leukemia / Stage IV Chronic Lymphocytic Leukemia / Stage IV Small Lymphocytic Lymphoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- GlaxoSmithKline Inc.
- MDS Nordion
- Dosage Forms
Form Route Strength Kit Intravenous Injection Intravenous 0.61 mCi/1mL Injection Intravenous 5.6 mCi/1mL Kit; solution Intravenous 14 mg / mL - Prices
Unit description Cost Unit Bexxar 131 iodine dosimetric 180.77USD ml Bexxar 14 mg/ml dosimetric 100.43USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 61 °C (FAB fragment), 71 °C (whole mAb) Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000) hydrophobicity -0.414 Not Available isoelectric point 8.68 Not Available
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Mhc class ii protein complex binding
- Specific Function
- This protein may be involved in the regulation of B-cell activation and proliferation.
- Gene Name
- MS4A1
- Uniprot ID
- P11836
- Uniprot Name
- B-lymphocyte antigen CD20
- Molecular Weight
- 33076.99 Da
References
- Goldenberg DM: The role of radiolabeled antibodies in the treatment of non-Hodgkin's lymphoma: the coming of age of radioimmunotherapy. Crit Rev Oncol Hematol. 2001 Jul-Aug;39(1-2):195-201. [Article]
- Dillman RO: Monoclonal antibody therapy for lymphoma: an update. Cancer Pract. 2001 Mar-Apr;9(2):71-80. [Article]
- Authors unspecified: Iodine-131 Tositumomab: (131)I-anti-B1 antibody, (131)I-tositumomab, anti-CD20 murine monoclonal antibody-I-131, B1, Bexxar, (131)I-anti-B1 antibody, iodine-131 tositumomab, iodine-131 anti-B1 antibody, tositumomab. BioDrugs. 2003;17(4):290-5. [Article]
- Friedberg JW, Fisher RI: Iodine-131 tositumomab (Bexxar): radioimmunoconjugate therapy for indolent and transformed B-cell non-Hodgkin's lymphoma. Expert Rev Anticancer Ther. 2004 Feb;4(1):18-26. [Article]
- Silverman DH, Delpassand ES, Torabi F, Goy A, McLaughlin P, Murray JL: Radiolabeled antibody therapy in non-Hodgkins lymphoma: radiation protection, isotope comparisons and quality of life issues. Cancer Treat Rev. 2004 Apr;30(2):165-72. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Beeson C, Butrynski JE, Hart MJ, Nourigat C, Matthews DC, Press OW, Senter PD, Bernstein ID: Conditionally cleavable radioimmunoconjugates: a novel approach for the release of radioisotopes from radioimmunoconjugates. Bioconjug Chem. 2003 Sep-Oct;14(5):927-33. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Not Available
- Specific Function
- Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complex...
- Gene Name
- FCGR2B
- Uniprot ID
- P31994
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor II-b
- Molecular Weight
- 34043.355 Da
References
- Glennie MJ, French RR, Cragg MS, Taylor RP: Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol. 2007 Sep;44(16):3823-37. [Article]
- Vaughan AT, Chan CH, Klein C, Glennie MJ, Beers SA, Cragg MS: Activatory and inhibitory Fcgamma receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain. J Biol Chem. 2015 Feb 27;290(9):5424-37. doi: 10.1074/jbc.M114.593806. Epub 2015 Jan 7. [Article]
Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:41