EXECUTIVE SUMMARY

CCH-A, A New Hemocyanin Subunit with Increased

Immunostimulating Properties

SUMMARY:  Siuta Consulting has been retained by NEOS (the only private technology transfer firm in Chile that represents the technology development of universities, industry, and private researchers) to identify partners for a novel subunit of hemocyanin that was isolated from the marine gastropod Concholepas concholepas by Drs. Alfredo Emilio De Ioannes and Maria Ines Becker in the Laboratory of Immunology, Department of Research and Development, BIOSONDA Corporation in Santiago, Chile.  This subunit, designated CCH-A (Concholepas concholepas hemocyanin subunit A), has potential applications as an immunostimulating agent in the innate or adaptive immune response or as an immunotherapeutic agent for the treatment of various cancers including melanoma, bladder, mammary and ovarian. 

BACKGROUND:  Hemocyanins are glycoproteins whose function is the transport of oxygen.  Hemocyanins isolated from mollusks and arthropods have been found to have a number of applications including (i) use as a carrier protein in the production of monoclonal and polyclonal antibodies in diagnostic kits and human therapy; and (ii) use as a non-specific immunostimulant in the therapy of some types of cancer.  To date, the best characterized hemocyanin was isolated from the California mollusk, keyhole limpet (Megathura crenulata), and is known as KLH (keyhole limpet hemocyanin).  It is one of the most commonly used carriers in the conjugation of peptides for antibody production and has been shown to be a clinically effective nonspecific immunomodulator for the treatment of superficial bladder cancer.  

These uses of KLH have led others to seek proteins with similar immunostimulant properties.  Drs. De Ioannes and Becker studied the hemocyanin from the marine gastropod Concholepas concholepas and identified a subunit, CCH-A, that was found to have potential applications as an immunostimulating agent and/or as an immunotherapeutic agent. 

TECHNOLOGY:  Hemocyanin from Concholepas concholepas consists of two subunits, CCH-A and CCH-B, with common and specific epitopes which provides it an extreme immunogenicity both at the level of innate and adaptive immune responses.  The complex molecular organization of the hemocyanin makes it an excellent carrier in the production of antibodies and in vaccine formulation.  It also provides it with non-specific immunostimulant properties when used as an immunotherapeutic agent in the treatment of cancer.  It is also a potent activator of NK cells. 

In addition, it has been found that the new CCH does not require additional divalent cations during the purification process in order to stabilize its structure.  This is a unique feature that has not been seen in other mollusk hemocyanins previously identified which requires Ca⁺² or Mg⁺² for stabilization. 

The investigators have found that the immune response to CCH-A subunit was significantly higher than that of CCH-B subunit or of the complete molecule.  CCH-A subunit was found to be effective for treating various cancers including melanoma, bladder, mammary and ovarian. 

PUBLICATIONS:  The following publications contain details of this research: 

P. De Ioannes, B. Moltedo, H. Oliva, R. Pacheco, F. Faunes, A. E. De Ioannes and M. I. Becker, Hemocyanin of the Molluscan Concholepas concholepas Exhibits an Unusual Heterodecameric Array of Subunits, J. Biol. Chem., 279 (25), 26134-26142 (2004).

H. Oliva, B. Moltedo, P. De Ioannes, F. Faunes, A. E. De Ioannes and M. I. Becker, Monoclonal Antibodies to Molluskan Hemocyanin from Concholepas concholepas Demonstrate Common and Specific Epitopes Among Subunits,  Hybridomas and Hybridomics, 21 (5), 365-374 (2002).

PATENT STATUS:  United States Patent 6,916,908 entitled "Product and Composition Containing a Concholepas concholepas Hemocyanin (CCH) Subunit, and a Method of Use Thereof" was issued on July 12, 2005.  It claims a disassociated CCH-A subunit isolated from hemocyanin of the marine gastropod Concholepas concholepas, where the CCH-A subunit has a molecular weight of about 404 kDa and is stable in the absence of Ca⁺² or Mg⁺².  The patent also claims the use of the CCH-A subunit as an immunostimulant agent in the innate or adaptive response or as an immunotherapeutic agent for the treatment of various cancers including melanoma, bladder, mammary and ovarian. 

LICENSE TERMS:  The CCH-A findings offer an excellent development opportunity.  While the project has demonstrated immunostimulating characteristics, support for current research is needed.  One area of interest is to obtain funds to continue the R&D of the product.  Others include research cooperation and a combined study of the CCH-A subunit.  As well, leading-edge technologies are desired for the increased study of the cloning and expression of the CCH-A immunogenic fragments. 

For commercial aspects, partners are sought for developing new applications and completing clinical trials, preferably, with vaccine or pharmaceutical experience that could better help develop the use of CCH-A for potent and applicable vaccines.