Alefacept

Identification

Summary

Alefacept is a recombinant fusion protein that binds CD2 and is used treat moderate to severe plaque psoriasis.

Generic Name
Alefacept
DrugBank Accession Number
DB00092
Background

Immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to the Fc (hinge, CH2 and CH3 domains) portion of human IgG1. Produced by CHO cells, mW is 91.4 kD.

Type
Biotech
Groups
Approved, Investigational, Withdrawn
Biologic Classification
Protein Based Therapies
Fusion proteins
Protein Structure
Protein Chemical Formula
C2306H3594N610O694S26
Protein Average Weight
51801.1 Da
Sequences
>Alefacept heavy chain 
CFSQQIYGVVYGNVTFHVPSNVPLKEVLWKKQKDKVAELENSEFRAFSSFKNRVYLDTVS
GSLTIYNLTSSDEDEYEMESPNITDTMKFFLYVLESLPSPTLTCALTNGSIEVQCMIPEH
YNSHRGLIMYSWDCPMEQCKRNSTSIYFKMENDLPQKIQCTLSNPLFNTTSSIILTTCIP
SSGHSRHRYALIPIPLAVITTCIVLYMNGILKCDRKPDRTNSNRVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPQVKFNWYVDGVQVHNAKTK
PREQQYNSTYRVVSVLTVLHQNWLDGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Alefacept light chain
MVAGSDAGRALGVLSVVCLLHCFGFISCFSQQIYGVVYGNVTFHVPSNVPLKEVLWKKQK
DKVAELENSEFRAFSSFKNRVYLDTVSGSLTIYNLTSSDEDEYEMESPNITDTMKFFLYV
LESLPSPTLTCALTNGSIEVQCMIPEHYNSHRGLIMYSWDCPMEQCKRNSTSIYFKMEND
LPQKIQCTLSNPLFNTTSSIILTTCIPSSGHSRHRYALIPIPLAVITTCIVLYMNGILKC
DRKPDRTNSN
Download FASTA Format
Synonyms
  • Alefacept
External IDs
  • ASP0485
  • BG-9273
  • BG-9712
  • BG9273
  • BG9712
  • LFA-3CD2
  • LFA-3TIP
  • LFA3TIP

Pharmacology

Indication

As an immunosuppressive drug, Alefacept can be used for treatment of moderate to severe chronic plaque psoriasis

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Interferes with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a role in the pathophysiology of chronic plaque psoriasis. Also causes a reduction in subsets of CD2+ T lymphocytes as well as CD4+ and CD8+ T lymphocytes.

Mechanism of action

Inhibits T-lymphocyte activation and production by binding to the CD2 lymphocyte antigen.

TargetActionsOrganism
AT-cell surface antigen CD2
inhibitor
antibody
regulator
Humans
ULow affinity immunoglobulin gamma Fc region receptor III-ANot AvailableHumans
ULow affinity immunoglobulin gamma Fc region receptor III-BNot AvailableHumans
Absorption

Bioavailability after IM administration is 63%.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

~270 hours

Clearance

Not Available

Adverse Effects
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Toxicity

While it has been found to cross the placenta in monkeys, it is not yet known if it also diffuses into breast milk.

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.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Abatacept.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Alefacept.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Alefacept.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Alefacept.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Alefacept.
Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AmevivePowder, for solution15 mg / 0.5 mLIntramuscularAstellas Pharma Inc2004-10-122012-12-01Canada flag
AmeviveKit15 mg/0.5mLIntramuscularAstellas Pharma Inc2003-01-302012-09-28US flag

Categories

ATC Codes
L04AA15 — Alefacept
Drug Categories
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
ELK3V90G6C
CAS number
222535-22-0

References

General References
  1. Koo JY, Bagel J, Sweetser MT, Ticho BS: Alefacept in combination with ultraviolet B phototherapy for the treatment of chronic plaque psoriasis: results from an open-label, multicenter study. J Drugs Dermatol. 2006 Jul-Aug;5(7):623-8. [Article]
  2. Krell JM: Use of alefacept and etanercept in 3 patients whose psoriasis failed to respond to etanercept. J Am Acad Dermatol. 2006 Jun;54(6):1099-101. [Article]
  3. Parrish CA, Sobera JO, Robbins CM, Cantrell WC, Desmond RA, Elewski BE: Alefacept in the treatment of psoriatic nail disease: a proof of concept study. J Drugs Dermatol. 2006 Apr;5(4):339-40. [Article]
PubChem Substance
46505772
RxNav
299635
ChEMBL
CHEMBL1201571
Therapeutic Targets Database
DAP000540
PharmGKB
PA164748040
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alefacept

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
4CompletedPreventionChronic Plaque Psoriasis1
4CompletedTreatmentAtopic Dermatitis1
4CompletedTreatmentChronic Plaque Psoriasis1
4CompletedTreatmentModerate to Severe Chronic Plaque Psoriasis1
4CompletedTreatmentPsoriasis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Astellas Pharma Inc.
  • Ben Venue Laboratories Inc.
  • Pierre Fabre
Dosage Forms
FormRouteStrength
KitIntramuscular15 mg/0.5mL
Powder, for solutionIntramuscular15 mg / 0.5 mL
Prices
Unit descriptionCostUnit
Amevive 15 mg vial1190.4USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.432Not Available
isoelectric point7.86Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Antibody
Regulator
General Function
Receptor binding
Specific Function
CD2 interacts with lymphocyte function-associated antigen (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytopla...
Gene Name
CD2
Uniprot ID
P06729
Uniprot Name
T-cell surface antigen CD2
Molecular Weight
39447.96 Da
References
  1. Chamian F, Lin SL, Lee E, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG, Lowes MA: Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis. J Transl Med. 2007 Jun 7;5:27. [Article]
  2. da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu YM, Hochman PS: Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol. 2002 May 1;168(9):4462-71. [Article]
  3. Larsen R, Ryder LP, Svejgaard A, Gniadecki R: Changes in circulating lymphocyte subpopulations following administration of the leucocyte function-associated antigen-3 (LFA-3)/IgG1 fusion protein alefacept. Clin Exp Immunol. 2007 Jul;149(1):23-30. Epub 2007 Apr 2. [Article]
  4. Goedkoop AY, de Rie MA, Picavet DI, Kraan MC, Dinant HJ, van Kuijk AW, Tak PP, Bos JD, Teunissen MB: Alefacept therapy reduces the effector T-cell population in lesional psoriatic epidermis. Arch Dermatol Res. 2004 Apr;295(11):465-73. Epub 2004 Feb 14. [Article]
  5. Ortonne JP: Clinical response to alefacept: results of a phase 3 study of intramuscular administration of alefacept in patients with chronic plaque psoriasis. J Eur Acad Dermatol Venereol. 2003 Jul;17 Suppl 2:12-6. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  3. da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu YM, Hochman PS: Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol. 2002 May 1;168(9):4462-71. [Article]
  4. Vaishnaw AK, TenHoor CN: Pharmacokinetics, biologic activity, and tolerability of alefacept by intravenous and intramuscular administration. J Pharmacokinet Pharmacodyn. 2002 Dec;29(5-6):415-26. [Article]
Kind
Protein
Organism
Humans
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. da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu YM, Hochman PS: Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol. 2002 May 1;168(9):4462-71. [Article]

Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:41