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

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Pharmacology

Indication

For treatment of non-Hodgkin's lymphoma (CD20 positive, follicular)

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Contraindications & Blackbox Warnings

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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	antibody	Humans
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

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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 software
Abacavir	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

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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
Bexxar Dosimetric	Injection	0.61 mCi/1mL	Intravenous	Glaxosmithkline Inc	2009-07-15	2014-02-13
Bexxar Therapeutic	Injection	5.6 mCi/1mL	Intravenous	Glaxosmithkline Inc	2009-07-15	2014-02-20
Bexxar Therapy	Kit; Solution	14 mg / mL	Intravenous	Glaxosmithkline Inc	2006-04-10	2014-07-31

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
Bexxar	Tositumomab (14 mg/1mL) + Tositumomab (14 mg/1mL)	Kit	Intravenous	Glaxosmithkline Inc	2009-07-15	2014-11-28

Chemical Identifiers

UNII: 0343IGH41U
CAS number: 208921-02-2

References

General References

Not Available

External Links

UniProt: P01857
Genbank: J00228
PubChem Substance: 46506662
RxNav: 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

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Details1. B-lymphocyte antigen CD20

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]

Details2. Low affinity immunoglobulin gamma Fc region receptor II-b

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

Tositumomab

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References

References