Display options
Share it on

Chem Sci. 2017 Mar 01;8(3):2056-2060. doi: 10.1039/c6sc03655d. Epub 2016 Nov 28.

Enabling the controlled assembly of antibody conjugates with a loading of two modules without antibody engineering.

Chemical science

Maximillian T W Lee, Antoine Maruani, Daniel A Richards, James R Baker, Stephen Caddick, Vijay Chudasama

Affiliations

  1. Department of Chemistry , University College London , 20 Gordon Street , London , WC1H 0AJ , UK . Email: [email protected] ; Tel: +44 (0)207 679 2077.

PMID: 28451324 PMCID: PMC5399535 DOI: 10.1039/c6sc03655d

Abstract

The generation of antibody conjugates with a loading of two modules is desirable for a host of reasons. Whilst certain antibody engineering approaches have been useful in the preparation of such constructs, a reliable method based on a native antibody scaffold without the use of enzymes or harsh oxidative conditions has hitherto not been achieved. The use of native antibodies has several advantages in terms of cost, practicality, accessibility, time and overall efficiency. Herein we present a novel, reliable method of furnishing antibody conjugates with a loading of two modules starting from a native antibody scaffold.

References

  1. Clin Cancer Res. 2004 Oct 15;10(20):7063-70 - PubMed
  2. Bioconjug Chem. 2005 Mar-Apr;16(2):346-53 - PubMed
  3. Nat Biotechnol. 2008 Aug;26(8):925-32 - PubMed
  4. Nat Biotechnol. 2009 Apr;27(4):331-7 - PubMed
  5. Org Biomol Chem. 2009 Sep 7;7(17):3361-71 - PubMed
  6. J Mol Biol. 2010 Jan 15;395(2):361-74 - PubMed
  7. Anal Chem. 2010 Jun 15;82(12):5219-26 - PubMed
  8. Curr Opin Chem Biol. 2010 Dec;14(6):803-9 - PubMed
  9. N Engl J Med. 2010 Nov 4;363(19):1812-21 - PubMed
  10. Chem Rev. 2011 Apr 13;111(4):2815-64 - PubMed
  11. Protein Eng. 1990 Aug;3(8):703-8 - PubMed
  12. Expert Opin Investig Drugs. 2011 Jun;20(6):733-44 - PubMed
  13. Chem Commun (Camb). 2011 May 21;47(19):5452-4 - PubMed
  14. Chem Commun (Camb). 2011 Aug 21;47(31):8781-3 - PubMed
  15. Clin Cancer Res. 2011 Oct 15;17(20):6437-47 - PubMed
  16. Curr Opin Pharmacol. 2012 Aug;12(4):398-402 - PubMed
  17. Nat Protoc. 2012 May 10;7(6):1052-67 - PubMed
  18. Nat Biotechnol. 2012 Jul 10;30(7):631-7 - PubMed
  19. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16101-6 - PubMed
  20. N Engl J Med. 2012 Nov 8;367(19):1783-91 - PubMed
  21. Clin Cancer Res. 2013 Feb 1;19(3):721-30 - PubMed
  22. Chem Biol. 2013 Feb 21;20(2):161-7 - PubMed
  23. Sci Rep. 2013;3:1525 - PubMed
  24. Nat Rev Drug Discov. 2013 May;12(5):329-32 - PubMed
  25. Blood. 2013 Aug 22;122(8):1455-63 - PubMed
  26. Chem Commun (Camb). 2013 Sep 25;49(74):8187-9 - PubMed
  27. Bioconjug Chem. 2014 Mar 19;25(3):510-20 - PubMed
  28. Bioconjug Chem. 2014 Mar 19;25(3):611-7 - PubMed
  29. Org Biomol Chem. 2014 Oct 7;12(37):7261-9 - PubMed
  30. Chem Commun (Camb). 2015 Mar 28;51(25):5279-82 - PubMed
  31. Bioorg Med Chem Lett. 2014 Dec 1;24(23):5357-63 - PubMed
  32. Pharm Res. 2015 Nov;32(11):3526-40 - PubMed
  33. Nat Commun. 2015 Mar 31;6:6645 - PubMed
  34. Mol Immunol. 2015 Oct;67(2 Pt A):142-52 - PubMed
  35. Chem Commun (Camb). 2015 Jul 7;51(53):10624-7 - PubMed
  36. Bioconjug Chem. 2015 Nov 18;26(11):2233-42 - PubMed
  37. Sci Transl Med. 2015 Aug 26;7(302):302ra136 - PubMed
  38. Chem Commun (Camb). 2015 Oct 25;51(83):15304-7 - PubMed
  39. Mol Pharm. 2015 Nov 2;12(11):3986-98 - PubMed
  40. Br J Cancer. 2016 Feb 16;114(4):362-7 - PubMed
  41. Nat Chem. 2016 Feb;8(2):114-9 - PubMed
  42. Drug Discov Today. 2016 May;21(5):850-5 - PubMed
  43. ACS Med Chem Lett. 2016 May 24;7(11):983-987 - PubMed
  44. Chem Sci. 2016 Jan 1;7(1):799-802 - PubMed
  45. Chem Sci. 2016 May 1;7(5):2954-2963 - PubMed
  46. Cancer Res. 1993 Jul 15;53(14):3336-42 - PubMed
  47. J Mol Biol. 1998 Feb 6;275(5):861-72 - PubMed

Publication Types