Cancer Vaccines from a Blue-Blooded Mollusk

Cancer Vaccines from a Blue-Blooded Mollusk
Signs of more treatments from the ocean

Along about 1,000 miles of coastline between Monterey, California, and Isla Asuncion, Mexico, a large mollusk lives just under the breaking waves of the Pacific Ocean.

Megathura crenulata, or the giant keyhole limpet, runs up to 10 inches in size, and uses an unusual molecule for breathing: hemocyanin. Instead of its red-blooded terrestrial oxygen carrier hemoglobin, hemocyanin is blue in color, carries a copper molecule instead of iron, and is used by marine snails and mollusks for gill-based respiration.

The molecule is fortuitous not only for the mollusk. Hemocyanin, especially keyhole limpet hemocyanin (KLH), also has long shown potential as a delivery vehicle for vaccines—especially cancer vaccines.
Vaccines work by mimicking the actions of a disease-causing cell or other foreign body. As they enter the blood, they’ll trigger a response by the body’s white blood cells (called T or B cells), which multiply and start to attack the foreign body. Once the vaccine is killed, the immune response will remain strong, often permanent.

But anti-cancer antigens are often too small to elicit an immune response. Without such a response, the body won’t be able to kill abnormal cells before they become full-fledged tumors. But KLH, which is a very, very large molecule, does elicit a slight immune reaction, resulting in T cells (and sometimes B cells) in the host that are specific to the cancer vaccine molecule. These KLH-vaccine combinations are undergoing clinical trials in a number of research institutions, for follicular lymphoma, non-Hodgkin lymphoma, glioblastoma, and melanoma, and bladder, prostate and ovarian cancer.

A biotechnology company in California, Stellar Biotechnologies, is harvesting KLH by farming keyhole limpets, and hopes that KLH will be approved as a drug (or in this case, a vaccine enhancer). While many natural substances are chemically tweaked for better performance, enhanced absorption by the human body, or other factors, KLH seems to work on its own. In addition, Stellar Biotech says, the KLH molecule is so large it defies artificial synthesis.

While the cancer-vaccine possibilities of KLH have been studied for years, its molecular structure was discovered only two years ago, which has created more potential for targeted vaccines. KLH is one of the largest carrier molecules in existence: resembling a hollow tube, it is assembled from two 500 kDa polypeptide subunits. By comparison, most proteins top out at about 200 kDa. KLH has eight functional units, each of which carries a single copper active site to reversibly bind to oxygen. This structure, as well as recent studies showing specific B cell homing activity for various KLH-antigen combinations, may finally provide a clinically available vaccine from the giant limpet.

The KLH story is a relatively new one in drug discovery. Many possible therapies may arise from organisms living in the ocean, but the discovery of these therapies has only seriously started over the past two decades or so. So, when in California or Mexico and you stumble upon a nearly foot-long flattish shell sticking to a rock, you might consider thanking it.

Photo: Wikimedia Commons

Kantele, A., Häkkinen, M., Zivny, J., Elson, C., Mestecky, J., & Kantele, J. (2011). Humoral Immune Response to Keyhole Limpet Haemocyanin, the Protein Carrier in Cancer Vaccines Clinical and Developmental Immunology, 2011, 1-6 DOI: 10.1155/2011/614383

Lieb, B., Gebauer, W., Gatsogiannis, C., Depoix, F., Hellmann, N., Harasewych, M., Strong, E., & Markl, J. (2010). Molluscan mega-hemocyanin: an ancient oxygen carrier tuned by a ~550 kDa polypeptide Frontiers in Zoology, 7 (1) DOI: 10.1186/1742-9994-7-14

Source:  United Academics Connect Science and Society

tumor vaccine, cancer immunology

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