My colleagues and I at CG Therapeutics, Inc., are at war with a molecule that brings much joy to this world but ironically much suffering and death as well. Human chorionic gonadotropin (hCG) is a protein hormone that is pretty well known, due to its place of honor as the substance that turns the pregnancy test kit blue (or purple or red or whatever color your kit turns). Rightly, a person ought to be overjoyed when the kit goes blue, but in some cases the news is met with less than thorough delight.
Furthermore, hCG has a downright evil side to it. When cancer cells begin to produce the pregnancy hormone, it helps them to spread and grow faster, while it simultaneously begins to shut down a person’s immune responses that would normally attack and kill the cancer. Somehow, the hormone of birth becomes the hormone of death. That cruel irony is the focus of work at CG Therapeutics. We intend to develop a vaccine that can block the function of hCG in cancer, giving patients a better fighting chance to resist and destroy the tumors that are trying to destroy them.
To create our vaccine, we dismantle the hCG molecule and inject inactive pieces of it into patients in a formulation that is much like a flu shot. Let’s have a look in detail. Above, the structure of whole hCG is shown with its two chains color coded. The alpha chain is shown in shades of pink and the beta chain is shown in shades of yellow. Click the image for a larger view. The alpha chain is common to a number of hormones besides hCG, for instance, thyroid stimulating hormone, which enhances the body’s energy metabolism, and also luteinizing hormone, which stimulates the sex drive among other things. We at CGT have no desire to monkey with either of those body functions, so we are not targeting the alpha chain.
However, the beta chain is another matter. Each of the hormones I just mentioned has its own unique beta chain, which pairs with the alpha chain to form what scientists call heterodimers, which possess the functional properties of the hormones. So, if you knock out the hCG beta chain, you can inactivate hCG without messing with levels of thyroid or sex hormones. That’s a nice idea, but how do you do it?
Have a look at the second image, where I’ve zoomed in on the right side of the hormone and color coded things a bit differently. Part of the formerly pink alpha chain has gone green, and part of the formerly yellow beta chain has gone blue, just like the test kit. You can see what I’m getting at by looking at one or the other of the two images, but if you’d like to try to get a real three-dimensional feel, try fusing the two images into one stereoscopic, 3-D view. How? Look in the dark blue space between the blue arrows and let your eyes unfocus. Think about looking far away, as if the dark blue background were the night sky. You should see two images of the arrows come together and fuse into one arrow. Now look down at the molecule. Is it in 3-D? I hope so. If you have trouble with this trick, click the image for a larger version. Try again. If that still doesn’t work try to adjust the size of the picture larger or smaller until the arrows have approximately 6.5 centimeters between them. That helps because it’s the average distance between people’s eyes and you want to be looking straight ahead, not crossing your eyes.
Anyway, that looping blue structure is the part of the hCG beta chain that we at CGT have been paying particular attention to. When a vaccine causes a patient to make antibodies that bind to that loop, the antibodies not only stick to hCG but they block its activity. That’s a pretty useful outcome for cancer patients because we’ve already demonstrated in clinical tests that many patients with advanced cancers live significantly longer when their bodies produce some “anti-loop” antibodies, as we call them.
We keep trying to increase the efficiency of our vaccine by subtly changing the nature of the loop fragment that we put into our formulation — a little longer, perhaps, or maybe shorter might work better. And there are other tricks to be tried with the loop that I don’t have time to go into here.
Finally, once a vaccine that blocks hCG is fully developed, we’re considering another use for it. It is quite possible that when formulated just right, this anti-cancer vaccine could also be an anti-pregnancy vaccine, stopping pregnancy before it starts. hCG is the pregnancy hormone, remember? Given that overpopulation is one of the gravest threats to the future of humanity, you may not be surprised at a phrase we at CGT occasionally quip in lighter moments of our otherwise arduous journey: “Once we’ve cured cancer, we’re going to save the world!”