The Power of KLH

Keyhole Limpet Hemocyanin (KLH) is a safe, potent immune-stimulating molecule, often used as a key ingredient in a new class of drugs known as active immunotherapies or therapeutic vaccines.

Active immunotherapies are engineered to stimulate the body’s own immune system to target and attack disease.  Unlike preventative vaccines, active immunotherapies are designed to generate an immune response against an existing disease or condition.  This is one of the fastest-growing sectors of pharmaceutical research and development today.

Intricate Topology of KLH Molecular Structure

A Complex Molecule

KLH is a very large, oxygen-carrying glycoprotein made of millions of atoms. 

The KLH molecular structure can be manipulated to generate multiple product configurations.  The high molecular weight native molecule and subunit of KLH are both excellent immune stimulants. Even a single subunit of KLH can be an effective vaccine carrier.

KLH is expressed in two subunit isoforms (KLH1 and KLH2) assembled into decamers and didecamers of 4 MDa to 8 MDa molecular weight. The subunit isoforms (approximately 400-600 kDa monomeric molecular weight) are each composed of 7 or 8 functional unit; each unit having an oxygen binding site of two copper atoms. The rich blue color of KLH is due to its copper-containing properties.

Different forms of KLH have distinctly different structural properties and believed to have different effects on the immune system.  The culture and processing of KLH can impact immunogenicity.  Recent preclinical data show that commercial source and form of KLH matter.

Well-Known & Versatile

KLH is widely used in immunological applications, both as an active pharmaceutical ingredient (API) in certain immunotherapies (a.k.a. therapeutic vaccines) and as a finished product for testing immune status in patients and research settings.

As an API, KLH is an effective and safe carrier molecule in active immunotherapies being developed for the treatment of cancer, inflammatory disease, rheumatoid arthritis, Alzheimer’s disease, and immune disorders.  The disease-targeting peptides, polysaccharides, and low molecular weight proteins in these therapies are not usually immunogenic enough to awaken the body’s immune system.  They require a carrier molecule or adjuvant to be effective.  KLH is a highly effective T-cell dependent carrier protein that induces MHC Class I and Class II-restricted immune responses via antigen presenting cells.  It is ideal in this role due to its immune-stimulating properties, large size, numerous sites for antigen conjugation, and safety profile.

KLH-based immunotherapies in development in the U.S. and internationally include TNF Kinoid vaccine for Crohn's disease, IFNα Kinoid vaccine for systemic lupus erythematosus, Globo-H-KLH vaccine for metastatic breast cancer, beta amyloid-targeting immunotherapy against Alzheimer’s disease, autologous vaccine for non-Hodgkin’s lymphoma, MUC-2-KLH vaccine for prostate cancer, and treatments for various other cancers and disorders.

KLH also has diagnostic applications as a finished injectable product.  It is extensively used by pharmaceutical companies and researchers as a safe, immune-stimulating antigen in drug immunotoxicology and assessment of immune status.  For example, KLH is a standard immunogen in T-Cell Dependent Antibody Response (TDAR), a functional assay used to assess an antibody response.  TDAR with KLH is widely recognized as a test for monitoring the effects of drugs on the immune system.

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