Product History
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)