Sustainable KLH Technologies for Growing Markets

KLH

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WHAT IS KLH?

Keyhole Limpet Hemocyanin (KLH) is a potent immunogenic high-molecular-weight protein; i.e. a substance that naturally induces an immune response.  KLH is a highly effective T-dependent carrier protein that induces MHC Class I and Class II-restricted immune responses via antigen presenting cells. 

KLH is an ideal carrier molecule for vaccine antigens (substances that promote the generation of antibody and cell-mediated immune responses) against cancers and infectious agents. The combination of an antigen against specific tumor cell-types, conjugated to the immunogenic KLH molecule, is the basis for a proven strategy for a new class of drugs known as therapeutic vaccines.

Potent yet safe in humans, KLH is highly prized as a critical component of certain therapeutic vaccines including ones for lymphoma, bladder, breast, colon and other cancers. Among the KLH-based therapeutic vaccines under development worldwide are:

  • Idiotype vaccines for lymphoma
  • TNFα vaccine for rheumatoid arthritis & Crohn's disease
  • VEGF vaccines for various cancers
  • Angiotensin vaccines for hypertension
  • Nicotine dependence vaccine

KLH also has diagnostic uses.  It is widely used by pharmaceutical companies and researchers as a safe, immune-stimulating antigen in drug screening, drug toxicology and assessment of immune status.  These diagnostic applications are a key focus of Stellar Biotechnologies' new product development.

The growing advancement of KLH-conjugated therapeutic vaccines and KLH-based diagnostic products is rapidly increasing the demand for GMP-grade KLH.

However, KLH is sourced only from a limited natural resource - Megathura crenulata, also known as the giant keyhole limpet, found only along a limited stretch of Pacific coastline from California to Baja, Mexico.

Stellar Biotechnologies was founded to address the urgent need for sustained commercial-scale supplies of high quality, GMP-grade KLH.  We developed leading practices, facilities and proprietary capabilities to address this need.

KLH is a very large, high molecular weight, oxygen-carrying metalloprotein from the hemolymph of the marine mollusc Megathura crenulata. The protein is expressed in two subunit isoforms (KLH1 and KLH2) of approximately 360,000 and 400,000 monomeric molecular weight. The KLH monomers are each composed of 7 or 8 functional unit domains; each functional unit contains an oxygen binding site containing two copper atoms. Both KLH isoforms assemble into native homo-didecamers of 4,000,000 to 8,000,000 molecular weight in hemolymph.

KLH's immunogenicity is partly attributed to the presence of unusual carbohydrate moieties, including unique Fuc(alpha1-3)GalNAc, Gal-(beta1-6)Man-, Gal(beta1-4)Fuc-, and Gal(beta1-4)Gal(beta(1-4)Fuc- structural motifs on N-glycans (Kantelhardt, 2002, Kurokawa et al. 2002, Wuhrer 2004).  Terminal mannose residues are mannose receptor ligands, suggesting that endocytosis of KLH via mannose receptor is a possible alternative mechanism for antigen presentation in KLH-based conjugate vaccines. KLH has been reported to stimulate dendritic cell maturation from human monocytes in processes possibly involving the mannose receptor (Presicce et al, 2007). 

Due to its exceptional size and unusual glycosylation, KLH cannot be easily synthesized, and is more efficiently and cost-effectively prepared by purification from the hemolymph of the source animal. 

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