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Identification
Name Alemtuzumab
Accession Number DB00087 (BIOD00109, BTD00109)
Type biotech
Groups approved
Description

Humanized monoclonal antibody specific to lymphocyte antigens. It is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H) that is directed against the 21-28 kD cell surface glycoprotein,CD52. The Campath-1H antibody is an IgG1 kappa with human variable framework and constant regions, and complementarity-determining regions from a murine (rat) monoclonal antibody (Campath-1G). Campath is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin.
Protein structure Db00087
Display: 3D Structure
Protein chemical formula C6468H10066N1732O2005S40
Protein average weight 145453.8000
Sequences 
>1CE1:H CAMPATH-1H:Heavy Chain 1
QVQLQESGPGLVRPSQTLSLTCTVSGFTFTDFYMNWVRQPPGRGLEWIGFIRDKAKGYTT
EYNPSVKGRVTMLVDTSKNQFSLRLSSVTAADTAVYYCAREGHTAAPFDYWGQGSLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

>1CE1:L CAMPATH-1H:Light Chain 1
DIQMTQSPSSLSASVGDRVTITCKASQNIDKYLNWYQQKPGKAPKLLIYNTNNLQTGVPS
RFSGSGSGTDFTFTISSLQPEDIATYYCLQHISRPRTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNR

>1CE1:H CAMPATH-1H:Heavy Chain 2
QVQLQESGPGLVRPSQTLSLTCTVSGFTFTDFYMNWVRQPPGRGLEWIGFIRDKAKGYTT
EYNPSVKGRVTMLVDTSKNQFSLRLSSVTAADTAVYYCAREGHTAAPFDYWGQGSLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

>1CE1:L CAMPATH-1H:Light Chain 2
DIQMTQSPSSLSASVGDRVTITCKASQNIDKYLNWYQQKPGKAPKLLIYNTNNLQTGVPS
RFSGSGSGTDFTFTISSLQPEDIATYYCLQHISRPRTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNR

>1bey_H|CAMPATH-1H|Humanized||VH-CH1 (VH(1-121)+CH1(122-210))|||||||219||||MW 23397.3|MW 23397.3|
QVQLQESGPGLVRPSQTLSLTCTVSGFTFTDFYMNWVRQPPGRGLEWIGFIRDKAKGYTT
EYNPSVKGRVTMLVDTSKNQFSLRLSSVTAADTAVYYCAREGHTAAPFDYWGQGSLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV

>1bey_L|CAMPATH-1H|Humanized||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(108-214))|||||||214||||MW 23571.3|MW 23571.3|
DIQMTQSPSSLSASVGDRVTITCKASQNIDKYLNWYQQKPGKAPKLLIYNTNNLQTGVPS
RFSGSGSGTDFTFTISSLQPEDIATYYCLQHISRPRTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>8005_H|alemtuzumab|||H-GAMMA-1 (VH(1-121)+CH1(122-219)+HINGE-REGION(220-220)+CH2(221-330)+CH3(331-437))|||||||437||||MW 47976.2|MW 47976.2|
QVQLQESGPGLVRPSQTLSLTCTVSGFTFTDFYMNWVRQPPGRGLEWIGFIRDKAKGYTT
EYNPSVKGRVTMLVDTSKNQFSLRLSSVTAADTAVYYCAREGHTAAPFDYWGQGSLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH
QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE
ALHNHYTQKSLSLSPGK

>8005_L|alemtuzumab|||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(108-214))|||||||214||||MW 23571.3|MW 23571.3|
DIQMTQSPSSLSASVGDRVTITCKASQNIDKYLNWYQQKPGKAPKLLIYNTNNLQTGVPS
RFSGSGSGTDFTFTISSLQPEDIATYYCLQHISRPRTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>1ce1_H|CAMPATH-1H|Humanized||VH-CH1 (VH(1-121)+CH1(122-219))|||||||220||||MW 23526.4|MW 23526.4|
QVQLQESGPGLVRPSQTLSLTCTVSGFTFTDFYMNWVRQPPGRGLEWIGFIRDKAKGYTT
EYNPSVKGRVTMLVDTSKNQFSLRLSSVTAADTAVYYCAREGHTAAPFDYWGQGSLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVE

>1ce1_L|CAMPATH-1H|Humanized||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(108-211))|||||||211||||MW 23282.0|MW 23282.0|
DIQMTQSPSSLSASVGDRVTITCKASQNIDKYLNWYQQKPGKAPKLLIYNTNNLQTGVPS
RFSGSGSGTDFTFTISSLQPEDIATYYCLQHISRPRTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNR

FASTA
Synonyms
  • alemtuzumab
Brand names
  • Campath
  • Campath (ILEX Pharmaceuticals LP)
  • MabCampath
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
CAS number 216503-57-0
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication Alemtuzumab (Campath) is a monoclonal antibody therapy used for treatment of B-cell chronic lymphocytic leukemia.
Pharmacodynamics Campath is used to treat leukemia by exploiting antibody mediated lysis of CD52 presenting cells. The CD52 antigen is a cell surface protein found on essentially all B and T lymphocytes, a majority of monocytes, macrophages and most granulocytes. The CD52 antigen is not present on erythrocytes or hematopoetic stem cells. In leukemia there is an excess of B and T cells, so Campath permits selective reduction of lymphocyte populations.
Mechanism of action Campath binds to the CD52 antigen present on most B and T lymphocytes. This binding leads to antibody-dependent lysis of leukemic cells.
Absorption Not Available
Volume of distribution
  • 0.18 L/kg
Protein binding Not Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system when bound to B or T lymphocytes
Route of elimination Not Available
Half life ~288 hrs
Clearance Not Available
Toxicity Not Available
Affected organisms Not Available
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Solution Intravenous
Prices
Unit description Cost Unit
Campath 30 mg/ml Solution (1 Box Contains Three 1ml Vials) 6179.24 USD box
Campath 30 mg/ml vial 2042.18 USD ml
Patents
Country Patent Number Approved Expires
Canada 1339198 1997-08-05 2014-08-05
Properties
State liquid
Melting point 61 oC (FAB fragment), 71 oC (whole mAb) – Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000).
Experimental Properties
Property Value Source
hydrophobicity -0.431 PhysProp
isoelectric point 8.76 Various sources
References
Synthesis Reference Not Available
General Reference
  1. Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, Waldmann H: Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. Blood. 1983 Oct;62(4):873-82. Pubmed
  2. Riechmann L, Clark M, Waldmann H, Winter G: Reshaping human antibodies for therapy. Nature. 1988 Mar 24;332(6162):323-7. Pubmed
  3. IGMT Link
  4. IGMT Link
  5. IGMT Link
External Links
Resource Link
PharmGKB PA10010 Link_out
Drug Product Database 2273993 Link_out
RxList http://www.rxlist.com/cgi/generic/campath.htm Link_out
Drugs.com http://www.drugs.com/cdi/alemtuzumab.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Alemtuzumab Link_out
ATC Codes
  • L01XC04
AHFS Codes
  • 10:00.00
PDB Entries
FDA label Not Available
MSDS show (39.4 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. CAMPATH-1 antigen

Pharmacological action: yes
Actions: antibody

May play a role in carrying and orienting carbohydrate, as well as having a more specific role

Organism class: human
UniProt ID: P31358 Link_out
Gene: CD52 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Gilliland LK, Walsh LA, Frewin MR, Wise MP, Tone M, Hale G, Kioussis D, Waldmann H: Elimination of the immunogenicity of therapeutic antibodies. J Immunol. 1999 Mar 15;162(6):3663-71. Pubmed
  2. James LC, Hale G, Waldmann H, Bloomer AC: 1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen. J Mol Biol. 1999 Jun 4;289(2):293-301. Pubmed
  3. Rawstron AC, Rollinson SJ, Richards S, Short MA, English A, Morgan GJ, Hale G, Hillmen P: The PNH phenotype cells that emerge in most patients after CAMPATH-1H therapy are present prior to treatment. Br J Haematol. 1999 Oct;107(1):148-53. Pubmed
  4. Rebello PR, Hale G, Friend PJ, Cobbold SP, Waldmann H: Anti-globulin responses to rat and humanized CAMPATH-1 monoclonal antibody used to treat transplant rejection. Transplantation. 1999 Nov 15;68(9):1417-20. Pubmed
  5. Hederer RA, Guntermann C, Miller N, Nagy P, Szollosi J, Damjanovich S, Hale G, Alexander DR: The CD45 tyrosine phosphatase regulates Campath-1H (CD52)-induced TCR-dependent signal transduction in human T cells. Int Immunol. 2000 Apr;12(4):505-16. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Geissinger E, Bonzheim I, Roth S, Rosenwald A, Muller-Hermelink HK, Rudiger T: CD52 expression in peripheral T-cell lymphomas determined by combined immunophenotyping using tumor cell specific T-cell receptor antibodies. Leuk Lymphoma. 2009 Jun;50(6):1010-6. Pubmed
  8. Quintas-Cardama A, O’Brien S: Targeted therapy for chronic lymphocytic leukemia. Target Oncol. 2009 Jan;4(1):11-21. Epub 2009 Jan 27. Pubmed

2. Low affinity immunoglobulin gamma Fc region receptor III-B

Pharmacological action: unknown

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 cytotoxicity and phagocytosis. May serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils

Organism class: human
UniProt ID: O75015 Link_out
Gene: FCGR3B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nagler A, Condiotti R, Lubina A, Deutsch VR: Enhancement of megakaryocytopoiesis by Campath-1G-treated natural killer cells. Bone Marrow Transplant. 1997 Oct;20(7):525-31. Pubmed
  2. Brett S, Baxter G, Cooper H, Johnston JM, Tite J, Rapson N: Repopulation of blood lymphocyte sub-populations in rheumatoid arthritis patients treated with the depleting humanized monoclonal antibody, CAMPATH-1H. Immunology. 1996 May;88(1):13-9. Pubmed
  3. Osterborg A, Werner A, Halapi E, Lundin J, Harmenberg U, Wigzell H, Mellstedt H: Clonal CD8+ and CD52- T cells are induced in responding B cell lymphoma patients treated with Campath-1H (anti-CD52). Eur J Haematol. 1997 Jan;58(1):5-13. Pubmed

3. Complement C1r subcomponent

Pharmacological action: unknown

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

Organism class: human
UniProt ID: P00736 Link_out
Gene: C1R Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

4. Complement C1q subcomponent subunit A

Pharmacological action: unknown

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) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes

Organism class: human
UniProt ID: P02745 Link_out
Gene: C1QA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

5. Complement C1q subcomponent subunit B

Pharmacological action: unknown

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) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes

Organism class: human
UniProt ID: P02746 Link_out
Gene: C1QB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

6. Complement C1q subcomponent subunit C

Pharmacological action: unknown

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) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes

Organism class: human
UniProt ID: P02747 Link_out
Gene: C1QC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

7. Low affinity immunoglobulin gamma Fc region receptor III-A

Pharmacological action: unknown

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 phagocytosis

Organism class: human
UniProt ID: P08637 Link_out
Gene: FCGR3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lin TS, Flinn IW, Modali R, Lehman TA, Webb J, Waymer S, Moran ME, Lucas MS, Farag SS, Byrd JC: FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia. Blood. 2005 Jan 1;105(1):289-91. Epub 2004 Jun 24. Pubmed

8. High affinity immunoglobulin gamma Fc receptor I

Pharmacological action: unknown

Binds to the Fc region of immunoglobulins gamma. High affinity receptor

Organism class: human
UniProt ID: P12314 Link_out
Gene: FCGR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

9. Low affinity immunoglobulin gamma Fc region receptor II-a

Pharmacological action: unknown

Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens

Organism class: human
UniProt ID: P12318 Link_out
Gene: FCGR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lin TS, Flinn IW, Modali R, Lehman TA, Webb J, Waymer S, Moran ME, Lucas MS, Farag SS, Byrd JC: FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia. Blood. 2005 Jan 1;105(1):289-91. Epub 2004 Jun 24. Pubmed

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

Pharmacological action: unknown

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 complexes and modulation of antibody production by B- cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis

Organism class: human
UniProt ID: P31994 Link_out
Gene: FCGR2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

11. Low affinity immunoglobulin gamma Fc region receptor II-c

Pharmacological action: unknown

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 modulation of antibody production by B-cells

Organism class: human
UniProt ID: P31995 Link_out
Gene: FCGR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on September 29, 2010 14:34

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.