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====Vaccine Attenuates Methamphetamine-Induced Disruptions in Thermoregulation and Activity in Rats====
====Vaccine Attenuates Methamphetamine-Induced Disruptions in Thermoregulation and Activity in Rats====
====Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food====
====Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food====
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+
====Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats====
==Materials and Methods==
==Materials and Methods==
===Synthesis of METH-like haptens===
===Synthesis of METH-like haptens===
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== Function ==
+
== Human Study ==
 +
===First Human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers===
== Disease ==
== Disease ==
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<ref name="Affinity improvement of a therapeutic antibody to methamphetamine and amphetamine through structure-based antibody engineering">PMID: 24419156 </ref>
<ref name="Affinity improvement of a therapeutic antibody to methamphetamine and amphetamine through structure-based antibody engineering">PMID: 24419156 </ref>
<ref name="Pharmacological effects of two anti-methamphetamine monoclonal antibodies">PMID: 25483484 </ref>
<ref name="Pharmacological effects of two anti-methamphetamine monoclonal antibodies">PMID: 25483484 </ref>
 +
<ref name="First Human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers">PMID: 25484042</ref>
 +
 +
<ref name="Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats">PMID: 26118833</ref>
 +
<ref name="Development and testing of AAV-delivered single-chain variable fragments for the treatment of methamphetamine abuse">doi:10.1371/journal.pone.0200060 </ref>

Revision as of 07:29, 8 December 2018

Contents

Immunotherapy for treating Methamphetamine Abuse

Introduction

Two major approaches to developing drug-specific immunotherapies: active and passive immunization

Antibody pharmacokinetics, pharmacodynamics and metabolism of therapeutic and diagnostic antibodies

Generation of anti-(+)methamphetamine antibodies during active immunization of rats

Vaccine Attenuates Methamphetamine-Induced Disruptions in Thermoregulation and Activity in Rats

Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food

Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats

Materials and Methods

Synthesis of METH-like haptens

Productions of anti-METH mAb, purification and formulation

Lead candidate selection for clinical development

Pharmacological effects of two anti-methamphetamine monoclonal antibodies

Human Study

First Human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers

Disease

Relevance

Structural highlights

Aromatic-Aromatic Interaction: A Mechanism of Protein Structure Stabilization

PDB ID 4lar

Drag the structure with the mouse to rotate
scFv6H4 in complex with amphetamine
Ligands: ,
Gene: IgG (LK3 transgenic mice)
Activity: ,
Related: 3gkz, 4laq, 4las
Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT
Coordinates: save as pdb, mmCIF, xml



This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>

References

[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]

[18] [19]



  1. ↑ Burley SK, Petsko GA. Aromatic-aromatic interaction: a mechanism of protein structure stabilization. Science. 1985 Jul 5;229(4708):23-8. PMID:3892686
  2. ↑ doi: https://dx.doi.org/10.1016/S1567-5769(00)00019-9
  3. ↑ Peterson EC, Owens SM. Designing immunotherapies to thwart drug abuse. Mol Interv. 2009 Jun;9(3):119-24. doi: 10.1124/mi.9.3.5. PMID:19592672 doi:http://dx.doi.org/10.1124/mi.9.3.5
  4. ↑ Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004 Nov;93(11):2645-68. doi: 10.1002/jps.20178. PMID:15389672 doi:http://dx.doi.org/10.1002/jps.20178
  5. ↑ Kosten T, Owens SM. Immunotherapy for the treatment of drug abuse. Pharmacol Ther. 2005 Oct;108(1):76-85. doi: 10.1016/j.pharmthera.2005.06.009. PMID:16023218 doi:http://dx.doi.org/10.1016/j.pharmthera.2005.06.009
  6. ↑ Hendrickson H, Laurenzana E, Owens SM. Quantitative determination of total methamphetamine and active metabolites in rat tissue by liquid chromatography with tandem mass spectrometric detection. AAPS J. 2006 Nov 22;8(4):E709-17. doi: 10.1208/aapsj080480. PMID:17233534 doi:http://dx.doi.org/10.1208/aapsj080480
  7. ↑ Peterson EC, Gunnell M, Che Y, Goforth RL, Carroll FI, Henry R, Liu H, Owens SM. Using hapten design to discover therapeutic monoclonal antibodies for treating methamphetamine abuse. J Pharmacol Exp Ther. 2007 Jul;322(1):30-9. doi: 10.1124/jpet.106.117150. Epub, 2007 Apr 23. PMID:17452421 doi:http://dx.doi.org/10.1124/jpet.106.117150
  8. ↑ Peterson EC, Laurenzana EM, Atchley WT, Hendrickson HP, Owens SM. Development and preclinical testing of a high-affinity single-chain antibody against (+)-methamphetamine. J Pharmacol Exp Ther. 2008 Apr;325(1):124-33. doi: 10.1124/jpet.107.134395. Epub , 2008 Jan 11. PMID:18192498 doi:http://dx.doi.org/10.1124/jpet.107.134395
  9. ↑ Gentry WB, Ruedi-Bettschen D, Owens SM. Development of active and passive human vaccines to treat methamphetamine addiction. Hum Vaccin. 2009 Apr;5(4):206-13. Epub 2009 Apr 20. PMID:19276653
  10. ↑ Celikel R, Peterson EC, Owens SM, Varughese KI. Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse - methamphetamine and 3,4 methylenedioxy-N-methylamphetamine. Protein Sci. 2009 Sep 16. PMID:19760665 doi:10.1002/pro.244
  11. ↑ Nanaware-Kharade N, Gonzalez GA 3rd, Lay JO Jr, Hendrickson HP, Peterson EC. Therapeutic anti-methamphetamine antibody fragment-nanoparticle conjugates: synthesis and in vitro characterization. Bioconjug Chem. 2012 Sep 19;23(9):1864-72. doi: 10.1021/bc300204n. Epub 2012 Aug , 28. PMID:22873701 doi:http://dx.doi.org/10.1021/bc300204n
  12. ↑ Miller ML, Moreno AY, Aarde SM, Creehan KM, Vandewater SA, Vaillancourt BD, Wright MJ Jr, Janda KD, Taffe MA. A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats. Biol Psychiatry. 2013 Apr 15;73(8):721-8. doi: 10.1016/j.biopsych.2012.09.010., Epub 2012 Oct 23. PMID:23098894 doi:http://dx.doi.org/10.1016/j.biopsych.2012.09.010
  13. ↑ Ruedi-Bettschen D, Wood SL, Gunnell MG, West CM, Pidaparthi RR, Carroll FI, Blough BE, Owens SM. Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food. Vaccine. 2013 Sep 23;31(41):4596-602. doi: 10.1016/j.vaccine.2013.07.038. Epub, 2013 Jul 29. PMID:23906885 doi:http://dx.doi.org/10.1016/j.vaccine.2013.07.038
  14. ↑ Peterson EC, Celikel R, Gokulan K, Varughese KI. Structural characterization of a therapeutic anti-methamphetamine antibody fragment: oligomerization and binding of active metabolites. PLoS One. 2013 Dec 5;8(12):e82690. doi: 10.1371/journal.pone.0082690. eCollection, 2013. PMID:24349338 doi:http://dx.doi.org/10.1371/journal.pone.0082690
  15. ↑ Thakkar S, Nanaware-Kharade N, Celikel R, Peterson EC, Varughese KI. Affinity improvement of a therapeutic antibody to methamphetamine and amphetamine through structure-based antibody engineering. Sci Rep. 2014 Jan 14;4:3673. doi: 10.1038/srep03673. PMID:24419156 doi:http://dx.doi.org/10.1038/srep03673
  16. ↑ Laurenzana EM, Stevens MW, Frank JC, Hambuchen MD, Hendrickson HP, White SJ, Williams DK, Owens SM, Gentry WB. Pharmacological effects of two anti-methamphetamine monoclonal antibodies. Supporting data for lead candidate selection for clinical development. Hum Vaccin Immunother. 2014;10(9):2638-47. doi: 10.4161/hv.29707. Epub 2014 Nov, 1. PMID:25483484 doi:http://dx.doi.org/10.4161/hv.29707
  17. ↑ Stevens MW, Henry RL, Owens SM, Schutz R, Gentry WB. First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers. MAbs. 2014;6(6):1649-56. doi: 10.4161/19420862.2014.976431. PMID:25484042 doi:http://dx.doi.org/10.4161/19420862.2014.976431
  18. ↑ Miller ML, Aarde SM, Moreno AY, Creehan KM, Janda KD, Taffe MA. Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats. Drug Alcohol Depend. 2015 Aug 1;153:29-36. doi: 10.1016/j.drugalcdep.2015.06.014., Epub 2015 Jun 19. PMID:26118833 doi:http://dx.doi.org/10.1016/j.drugalcdep.2015.06.014
  19. ↑ Hay CE, Gonzalez GA 3rd, Ewing LE, Reichard EE, Hambuchen MD, Nanaware-Kharade N, Alam S, Bolden CT, Owens SM, Margaritis P, Peterson EC. Development and testing of AAV-delivered single-chain variable fragments for the treatment of methamphetamine abuse. PLoS One. 2018 Jun 29;13(6):e0200060. doi: 10.1371/journal.pone.0200060., eCollection 2018. PMID:29958300 doi:http://dx.doi.org/10.1371/journal.pone.0200060
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