Putting Nature to Work to Find Cancer

07-Nov-2013

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Pus from a cowpox sore. Gross? Yes. But it also played the starring role in a brilliant science experiment more than 200 years ago, the results of which would ultimately save millions of lives.
Scholars believe the disease called smallpox first appeared around 10,000 BCE, in the early agricultural settlements of northeastern Africa. It then spread throughout the developing world via merchants and trade routes and military conquests, devastating our species for many centuries thereafter. In 18thcentury Europe, smallpox killed approximately 400,000 people annually. That’s equivalent to wiping out the entire population of Atlanta every year. Those who did survive the scourge were left with disfiguring scars and often without sight.
It was common knowledge for hundreds of years that survivors of smallpox were subsequently immune to the disease. And the process of inoculation (also known as “variolation”)—which involved the risky subcutaneous delivery of the smallpox virus into an arm or leg of a nonimmune individual—was well known in Europe by the 1720s. But it was not until a man named Edward Jenner came along in 1796 that the fight against smallpox would take a giant leap forward.
Jenner hypothesized that cowpox—a much less dangerous disease than smallpox—could induce immunity to smallpox. To test his idea, Jenner scraped pus from a milkmaid’s cowpox blisters and used it to inoculate an eight-year-old boy named James Phipps (after obtaining his parents’ permission, of course). A far cry from the elaborate clinical trials of today, isn’t it? But it worked. Phipps developed a mild fever and some discomfort from the injection but recovered quickly and was subsequently shown to be immune to smallpox.
Jenner’s work marked the beginning of the modern practice of vaccination. And vaccines have saved millions of lives since.
Normally, when we refer to these types of traditional vaccines, we’re talking about killed or weakened microbes (or parts of microbes), i.e., pathogens that stimulate an immune response without causing the disease (hopefully). According to the National Cancer Institute:

When the immune system encounters these substances through vaccination, it responds to them, eliminates them from the body, and develops a memory of them. This vaccine-induced memory enables the immune system to act quickly to protect the body if it becomes infected by the same microbes in the future.

In other words, the vaccines that we know today are preventative. They are meant to keep you from getting a disease. But scientists are developing new types of vaccines called therapeutic vaccines; and as the name implies, these vaccines are intended to actually cure diseases.
One of the diseases scientists hope to treat with these new types of vaccines is cancer.
Cancer drug development today is focused on targeted therapies that go beyond the traditional crude mix of “slash, burn, and poison” (surgery, radiation, and chemotherapy) to deliver therapeutic effects with reduced toxicity. On paper, cancer vaccines are the perfect addition to the more targeted, less toxic drug arsenal. Simply “train” a patient’s immune system to recognize and destroy tumor cells, and let nature do the rest.
The notion of using the immune system to launch an attack on cancer has actually been around for some time. The basic idea is to rouse the immune system by presenting it with antigens associated with tumor cells. Ideally, the immune system would not only seek out and destroy the tumor cells, but it would remember the abnormal antigens and be ready to mount a new attack if the tumor were to recur.
It’d be great if it were just that simple. In practice, however, it’s been far more complicated.
The most difficult challenge is the fact that a tumor is not really a pathogen; at its core, it’s a collection of aggressively growing cells that can’t stop dividing. It’s not a foreign invader, nor does it “infect” healthy cells, as do bacteria and viruses. So launching the immune system against cancer cells essentially involves turning the body’s defense mechanisms against a part of itself. And that’s not the only practical problem with cancer vaccines. For instance, there’s also the relatively recent discovery that tumors can somehow actively induce local immunosuppression.
Thus, the annals of biotech R&D are littered with more than a decade’s worth of promising therapeutic cancer vaccines that failed to show clinical efficacy. To date, in fact, only one such vaccine has come to market to help treat cancer in humans, Dendreon’s Provenge. Provenge became the first FDA-approved therapeutic cancer vaccine in April of 2010. While the drug represents a breakthrough technology (and remains the only such drug in use today), it’s a completely uneconomic solution to the problem. Here’s why: The vaccine is created by isolating white blood cells from a patient’s blood through a procedure called “leukapheresis.” These cells are shipped off to the company’s lab, where they are exposed to chemicals that turn them into special cells called dendritic cells, then cultured with certain proteins designed to trigger an immune response against prostate cancer. Finally, the dendritic cells are shipped back to the physicia n and intravenously administered to the patient. In other words, the drug is customized to each patient. Not only that, Dendreon can only produce a single patient-specific dose at a time. Needless to say, manufacturing costs of Provenge—and thus the cost to the end user—are extremely high.
Improvements are on the horizon, however.
A company called ImmunoCellular Therapeutics (IMUC) is also developing a patient-specific therapeutic cancer vaccine that has shown great promise in clinical trials. The difference is that it can manufacture approximately 20 doses at once for the patient, compared to Dendreon’s one.
It doesn’t stop there. Most of the therapeutic cancer vaccines now in development are designed to be off the shelf rather than produced for each patient, and are tailored to groups with perhaps multiple tumor types rather than individuals. Canada-based Immunovaccine, for example, has a drug in development that combines seven antigens found in breast, ovarian, and prostate cancers in a sustained-release formulation.
Meanwhile, over at Harvard, researchers are attempting to overcome the logistical challenges of therapeutic cancer vaccines in a whole different way—by creating an implantable device designed to recruit and reprogram immune cells to attack tumors. If this is successful, there would be no need to extract cells from the patient and ship them off to a lab to be primed for tumor targeting, as is the case with Provenge. Phase I safety data for this approach are not due for a couple of years, but it’s another exciting avenue being explored.
Of course, we can still expect to see big failures on the road to a robust pipeline of safe and effective therapeutic cancer vaccines (the widely hyped GlaxoSmithKline melanoma vaccine candidate MAGE-A3 just went bust in late-stage trials), but the future is still bright. Citigroup analyst Andrew Baum reckons that oncology immunotherapies, which include vaccines and therapeutic antibodies, will generate sales of up to $35 billion a year within the next decade and in the process will create the biggest drug class in history, according to Reuters.

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