History of KLH and biosyn keyhole limpet hemocyanins (IMMUCOTHEL®, VACMUNE®)

  • 1973 first clinical indication to efficacy (Olsson, USA)
  • 1977 first animal experiment (Klippel, Germany)
  • 1983 confirmation of the effect by animal model (Lamm, USA)
  • 1984 foundation biosyn & start of pharmaceutical and clinical development
  • 1993 KLH as vaccine carrier, drug master file (FDA)
  • 1994 foundation of biosyn corp. Carlsbad, Cal. USA & application for marketing authorization in EC countries
  • 1997 first marketing authorization in The Netherlands
  • 1997 first 3D reconstruction of KLH at 15 Å resolution
  • 1999 evaluation of the gene sequence encoding for KLH
  • 2000 first recombinant protein
  • 2001 marketing authorization in Austria and South Korea
  • 2002 Determination of the major antigenic motif of Schistosoma mansoni glycolipids implicated in infection sera and Keyhole Llimpet Hemocyanin cross-reactivity
  • 2002 Determination of a novel and unique type of KLH sugar constitutents
  • 2004/5 marketing authorization in Argentina
  • 2005 KLH significantly reduces cellular proliferation in melanoma and inhibits the growth of human breast and pancreas cancer in vitro
  • 2005  First detailed structural data on the KLH carbohydate entities responsible for cross-reactivity with glycoconjugates from Schistosoma mansoni
  • 2006 recombinant expression of KLH substructures in the prokaryotic system E. coli
  • 2007 KLH potentiates standard immunotherapy for melanoma in vivo
  • 2008 KLH induces the activation and maturation of human dendrictic cells (endowed with the ability to stimulate cell-mediated immune response)
  • 2008 recombinant expression of KLH substructures in insect and mammalian expression systems
  • 2008 First x-ray structure of a functional unit of KLH
  • 2009 first 9 Å CryoEM structure and molecular model of KLH (reveal the interfaces and intricate topology of the 160 functional units)