Tositumomab

Identification

Name
Tositumomab
Accession Number
DB00081  (BTD00085, BIOD00085, DB09557)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

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).

Protein structure
Db00081
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
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Tositumomab I-131K1KT5M40JC192391-48-3Not applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bexxar DosimetricInjection0.61 mCi/1mLIntravenousGlaxosmithkline Inc2009-07-152014-02-13Us
Bexxar TherapeuticInjection5.6 mCi/1mLIntravenousGlaxosmithkline Inc2009-07-152014-02-20Us
Bexxar TherapyKit; Solution14 mgIntravenousGlaxosmithkline Inc2006-04-102014-07-31Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
BexxarTositumomab (14 mg/1mL) + Tositumomab (14 mg/1mL)KitGlaxosmithkline Inc2009-07-152014-11-28Us
BexxarTositumomab (14 mg/1mL) + Tositumomab (14 mg/1mL)KitGlaxosmithkline Inc2009-07-152014-11-28Us
International/Other Brands
Bexxar (Corixa Corp)
Categories
UNII
0343IGH41U
CAS number
208921-02-2

Pharmacology

Indication

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

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.

TargetActionsOrganism
AB-lymphocyte antigen CD20
antibody
Human
ULow affinity immunoglobulin gamma Fc region receptor III-BNot AvailableHuman
UComplement C1r subcomponentNot AvailableHuman
UComplement C1q subcomponent subunit ANot AvailableHuman
UComplement C1q subcomponent subunit BNot AvailableHuman
UComplement C1q subcomponent subunit CNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor III-ANot AvailableHuman
UHigh affinity immunoglobulin gamma Fc receptor INot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-aNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-bNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-cNot AvailableHuman
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]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when (R)-warfarin is combined with Tositumomab.
(R)-warfarinThe risk or severity of bleeding can be increased when (R)-warfarin is combined with Tositumomab.
(S)-WarfarinThe risk or severity of bleeding and hemorrhage can be increased when (S)-Warfarin is combined with Tositumomab.
(S)-WarfarinThe risk or severity of bleeding can be increased when (S)-Warfarin is combined with Tositumomab.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Tositumomab is combined with 2-Methoxyethanol.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when 4-hydroxycoumarin is combined with Tositumomab.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when 4-hydroxycoumarin is combined with Tositumomab.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Tositumomab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbacavirTositumomab may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Tositumomab is combined with Abatacept.
Food Interactions
Not Available

References

General References
Not Available
External Links
UniProt
P01857
Genbank
J00228
PubChem Substance
46506662
ChEMBL
CHEMBL1201604
Therapeutic Targets Database
DAP000384
PharmGKB
PA164748364
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tositumomab
ATC Codes
V10XA53 — Tositumomab/iodine (131i) tositumomab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentFollicular Lymphoma (FL)1
1CompletedTreatmentLymphoma, B-Cell / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)3
1Unknown StatusTreatmentChronic Lymphocytic Leukaemia (CLL)1
1Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)1
1, 2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Active Not RecruitingTreatmentLymphoma, B-Cell1
2Active Not RecruitingTreatmentMalignant Lymphomas1
2Active Not RecruitingTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentFollicular Lymphoma (FL)1
2CompletedTreatmentLymphoid Leukemia in Remission / Stage I Chronic Lymphocytic Leukemia / Stage II Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage III Small Lymphocytic Lymphoma / Stage IV Chronic Lymphocytic Leukemia / Stage IV Small Lymphocytic Lymphoma1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMantle Cell Lymphoma (MCL)2
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)9
2TerminatedTreatmentFollicular Lymphoma (FL)1
2TerminatedTreatmentFollicular Lymphoma (FL) / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)1
3CompletedTreatmentLymphoma, B-Cell / Lymphoma, Large-Cell, Immunoblastic / Non-Hodgkin's Lymphoma (NHL)1
3CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
3WithdrawnTreatmentFollicular Lymphoma (FL) / Lymphoma, Large-Cell, Follicular / Lymphoma, Small Cleaved-Cell, Follicular / Non-Hodgkin's Lymphoma (NHL)1
Not AvailableUnknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • GlaxoSmithKline Inc.
  • MDS Nordion
Dosage forms
FormRouteStrength
Kit
InjectionIntravenous0.61 mCi/1mL
InjectionIntravenous5.6 mCi/1mL
Kit; solutionIntravenous14 mg
Prices
Unit descriptionCostUnit
Bexxar 131 iodine dosimetric180.77USD ml
Bexxar 14 mg/ml dosimetric100.43USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.414Not Available
isoelectric point8.68Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:11418316]
  2. Dillman RO: Monoclonal antibody therapy for lymphoma: an update. Cancer Pract. 2001 Mar-Apr;9(2):71-80. [PubMed:11879282]
  3. 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. [PubMed:12899647]
  4. 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. [PubMed:14748653]
  5. 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. [PubMed:15023434]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. 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. [PubMed:13129395]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent...
Gene Name
FCGR3B
Uniprot ID
O75015
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-B
Molecular Weight
26215.64 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type peptidase activity
Specific Function
C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.
Gene Name
C1R
Uniprot ID
P00736
Uniprot Name
Complement C1r subcomponent
Molecular Weight
80118.04 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proe...
Gene Name
C1QA
Uniprot ID
P02745
Uniprot Name
Complement C1q subcomponent subunit A
Molecular Weight
26016.47 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proe...
Gene Name
C1QB
Uniprot ID
P02746
Uniprot Name
Complement C1q subcomponent subunit B
Molecular Weight
26721.62 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proe...
Gene Name
C1QC
Uniprot ID
P02747
Uniprot Name
Complement C1q subcomponent subunit C
Molecular Weight
25773.56 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as...
Gene Name
FCGR3A
Uniprot ID
P08637
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-A
Molecular Weight
29088.895 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor signaling protein activity
Specific Function
High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
Gene Name
FCGR1A
Uniprot ID
P12314
Uniprot Name
High affinity immunoglobulin gamma Fc receptor I
Molecular Weight
42631.525 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized ...
Gene Name
FCGR2A
Uniprot ID
P12318
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-a
Molecular Weight
35000.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane signaling receptor activity
Specific Function
Receptor for the Fc region of complexed immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulat...
Gene Name
FCGR2C
Uniprot ID
P31995
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-c
Molecular Weight
35577.96 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2018 19:13