Wouldn’t it be wonderful if we could build smart bombs for cancer? Then we could selectively kill cancer while sparing the body. Does this sound like a Star Trek movie? Maybe, but some of these therapies already exist and more are in the pipeline every day.
In the first part of this two-part article we focused on a method that specifically targets tumors, cancer vaccines. With this article we explore two other methods of targeting cancer, including monoclonal antibodies and nanoparticles. What all of these therapies share is a targeting of the cancer by taking advantage of something unique to the tumor.

As a reminder, cancer vaccines use the exquisite specificity of our immune system to target a tumor. Keep in mind that the immune system’s specificity is an important part of how it works and is vital to our very health. So, when you think of the immune system, don’t just think of it as a protective system, think of it as a very specific protective system. This concept also lies at the heart of many real and potential immunotherapies.

One such immunotherapy uses monoclonal antibodies. What are antibodies? They are proteins produced by white blood cells called plasma cells. Antibodies have the unique ability to stick to specific targets in a nearly permanent manner. Once stuck, antibodies can both interfere with the function of the target and attract white blood cells.

Typically, when the immune system makes antibodies to fight an infection, it makes many different types. Antibodies produced this way are called polyclonal because they come from many different plasma cells. Monoclonal antibodies, on the other hand, are produced in a petri dish. Each little well in the dish contains a single plasma cell. Each of these plasma cells will produce a single type of antibody with a unique target. Thus monoclonal antibodies are designed to target one specific thing.

So how can monoclonal antibodies be used in cancer therapy? Simple, a cancer monoclonal antibody will specifically attach to, or target, cancer cells within the body. Once stuck to the cancer cell(s) they should attract the whole immune system to the cancer. Like with cancer vaccines, the only hold up for cancer monoclonal antibodies is finding a specific target.

In human oncology, many monoclonal antibody therapies already exist. Many of these work so well that they have become considered the standard of care for cancer. In veterinary medicine we, currently have two FDA approved monoclonal antibodies. Both of these are labeled for dogs that have lymphoma. Unfortunately, these new dog monoclonal antibody therapies are not as effective as we had hoped, and they require more traditional therapies to achieve full efficacy.

Because of their unique ability to specifically bind to cancer cells, new uses for these monoclonal antibodies are being explored every day. For example, they may act as a perfect delivery vehicle. Picture this: a cancer drug, hooked to a cancer monoclonal antibody. This drug-antibody complex is then sent to out find the cancer. Once it has found the cancer, it delivers its drug payload, thus becoming a cancer smart-bomb. In the future, expect to see this kind of use for monoclonal antibodies in cancer medicine.

Immunotherapies are only one method to provide specific targeting of cancer therapy. There are many others actively being explored in cancer research. For example, use of nanoparticles in cancer medicine. These tiny particles get their name because they are truly nanometers in size. Nanoparticles can be made out of many different compounds, including silicone and metals. What makes them interesting in cancer medicine is that nanoparticles appear to have a unique ability to accumulate preferentially in tumors. Imagine, if a nanoparticle could be harnessed to carry cancer therapies, they could become another form of a cancer smart-bomb.

Why are nanoparticles specifically attracted to tumors? It is through the unique nature of tumor blood vessels. To understand that, let’s first explore normal blood vessels. Most normal vessels are built uniformly and methodically. This is crucial, because if a cell gets farther than 2 microns from a blood vessel, it starts die from lack of nutrients and the buildup of waste products. To facilitate this delivery and waste–removal, blood vessels have pores built within their walls.

Unlike normal blood vessels, tumor blood vessels are often abnormal due to their rushed and haphazard growth. One of the most striking features of these abnormal vessels is their pores: they are very irregular and quite large. So how do nanoparticles preferentially accumulate in tumors? Due to nanoparticles’ size, they cannot transverse into normal tissues through the small pores in the blood vessels. However, nanoparticles have no trouble moving through the large, abnormal pores found in tumor blood vessels.

In the over ten years of research focusing on nanoparticles in cancer, no obvious or overt toxicity has been found from these particles. The next phase of this research will be more challenging, involving how to get the particles to release their pay load in the tumor to kill the cancer cells. Delivery ability of nanoparticles may be years in the making. At this point these little guys are shaping up to be the perfect delivery vehicle for cancer drugs.

There may be other potential uses for nanoparticles in cancer medicine. For example, the Cancer Center at Olympia Veterinary Specialists is about to institute a clinical trial using these nanoparticles in combination with lasers. It is a clinical trial designed to use all the special attributes of nanoparticles, not just their ability to accumulate in a tumor.

If a nanoparticle has metal within its structure, it will vibrate or move around when exposed to certain wave lengths of light (such as produced by lasers). When the nanoparticle vibrates, it will generate heat. If a tumor is filled nanoparticles and that tumor is exposed to the right wavelength of light, in theory the nanoparticles will start heating up the tumor. Heat has the ability to kill cancer cells directly or through programmed cell death, called apoptosis (ae-pop-toe-sis). Either way, the heat should cause cancer cells to die. If this is true, we will have found a new way to use nanoparticles to specifically kill the cancer.

What does the future of cancer therapy hold? It is full of hope, built on imagination and science. In these last two articles I outlined several therapies that not 10 years ago would have seemed the stuff of science fiction. In the decade to come we will undoubtedly see even more space-age advances that today seem impossible. Regardless of the approach, the common theme will be how to specifically target the cancer while sparing the body and improving quality of life for all cancer patients.

By Lisa Parshley, DVM,PHD,DACVIM Olympia Veterinary Specialists (OVS). To learn more about OVS, visit their website here.