A protein called Keyhole Limpet Hemocyanin (KLH) could play a key role in treating many different types of cancers. KLH can be used to direct the body to attack the cancer cells, and it also has important applications in immune response testing and immunotoxicology. But the molecule is harvested from a rare mollusk, and is extremely expensive, selling for thousands of dollars per gram. A company called Stellar Biotechnologies has found a way to harvest KLH without killing the mollusks, constituting a major advance for cancer treatment. In an interview with Sander Olson, Stellar Vice-President Dr. Herbert Chow, Ph.D, describes the considerable potential of this protein.
Herbert Chow, Ph.D, interview
Question: How did you first find out about the Keyhole Limpet Hemocyanin (KLH)?
I have known of the unique and extremely valuable properties of KLH since my days as a student of immunology many years ago. I have been with Stellar working on KLH related products for about 18 months. It is a large molecule that is harvested from the blood of a very rare ocean mollusk. This mollusk resides from central California to Baja Mexico. This mollusk produces a glycoprotein – a protein sheathed in a sugar molecule. This is one of the largest molecules ever found in the biological world. Due to its sheer size, it cannot be synthetically made, and can only be harvested from this mollusk. This molecule, which we call KLH, is extremely valuable and can be used in vaccines as well as other therapies.
Question: The company you work for, Stellar Biotechnologies, has found a way to harvest this molecule from the mollusks without killing the creatures. Why is that important?
Stellar has found a way to harvest the molecule without killing the mollusk – every other extraction process ends up killing the mollusk. This mollusk is very rare, is only found off the coast of California, and its numbers in the natural world are declining. So sustainability is a critically important issue. Stellar is the only company that has found a way to successfully and sustainably harvest the KLH molecule.
Question: Why exactly is this molecule so valuable?
KLH has important diagnostic and therapeutic applications. First and foremost, KLH is a potent immune stimulant. We can inject it into humans or other animals and get a specific immune response with no side effects. So we can use this molecule as a carrier to direct the patient’s immune response. But KLH also has potent diagnostic applications. It is a standard antigen to look for immunotoxicities – to test for unwanted side effects of drugs.
Question: Are these limpets difficult to cultivate? How long do they live?
These mollusks are long-lived, slow growing creatures. They can be temperamental, and cultivating them is not easy. But Stellar has acquired this expertise, and we are now growing large numbers of these mollusks.
Question: KLH is an immunogenic carrier protein. What is that, and why is it so useful?
A carrier protein is generally a large molecule on which one can attach a smaller molecule. It is easy to attach other molecules to the massive KLH molecule. We can then present this molecule to the body, which can react to the antigens that are attached to the KLH molecule. In this way we create an immune response.
Question: So there are no side-effects to KLH?
KLH has been exhaustively tested and found to be an extremely safe and benign molecule. There are essentially no side effects, even at large doses.
Question: How many KLH-based therapies are currently being explored?
There are a number of cancer vaccines in development that use KLH. But there are also Alzheimer vaccines and nicotine-dependency vaccines, as well as veterinary vaccines. Most vaccines require some form of immune boosting, and KLH does this.
Question: What is the current cost per gram of the KLH? To what extent can the cost be reduced?
Cost are dependent upon volume and purity requirements, but it is in the thousands to tens of thousands of dollars per gram range at most quantities in use today. Costs will go down as we scale-up production. We anticipate that the market for KLH will rapidly increase, and we are prepared to increase production as necessary.
Question: What quantities of KLH can Stellar Biotechnologies currently produce?
We have created a protocol and infrastructure that will allow us to produce multi-gram quantities over a few days. We aren’t currently capable of producing kilogram quantities, except over a period of 6 months to a year, but we should attain that monthly capability within the next few years.
Question: How many different molecular weights of KLH are there?
Fragmentation of the native molecule results into at least 6 or 7 different molecular weight species of KLH. Different molecular weights may have different stimulatory effects to the immune system. We are becoming increasingly adept at manipulating and modifying the KLH molecule in order to tailor its properties and effects.
Question: Is the KLH molecule directly therapeutic?
For the most part it isn’t. There has been one case where KLH has applications in bladder cancer. In that case, it promotes enough inflammation to do collateral damage to the cancer cells. But for the most part we are using the KLH molecules to “wake up” the immune system to the vaccine portion, which usually is poorly immunogenic.
Question: Could this approach be used to stimulate the body’s immune system against any type of cancer?
Yes. At this point, the evidence suggests that regardless of whether we are dealing with a carbohydrate, a protein, or a glycoprotein, we should be able to use KLH to get the immune system to recognize it. So we have only scratched the surface of the true capabilities of KLH.
Question: Could a competitor create a synthetic molecule that would perform the same functions as KLH?
Creating a synthetic molecule with the same properties as KLH would be extremely difficult. This is one of the largest molecules that exists. The genomes for KLH are fragmented in many places. In years to come the only viable way to supply KLH is through direct extractions of material from the animal itself.
Question: How frequently can the KLH be extracted from the mollusks?
Currently, 3-4 times per year. Stellar Biotechnologies is the only company with patent-protected methodology to extract the KLH without killing the mollusk. We let them rest after extraction. As demand goes up, we will increase our capacity, so that we are tapping an ever larger number of animals. We can induce spawning of these animals, so we can steadily increase the population of limpets. This is important since the natural population is declining.
Question: To what extent will the market for KLH will increase during the next five years?
KLH is already a coveted molecule, and its value to the biotechnology and pharmaceutical industries keeps increasing as novel uses continue to be found. Although it is premature to talk at this point of curing cancer, we do envision these vaccines prolonging life and increasing survival rates for an ever growing number of cancers. We see a straightforward path for the next decade where we maximize the gain of these vaccines while minimizing the side effects. KLH is or will likely become the preferred molecule for antibody generation, immune response testing, and immunotoxicology, and the market for this molecule could grow exponentially.
The interviewer owns stock in Stellar Biotechnologies.