Cells Gone Wild: Creating Vaccines that Target Cancer

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"Now that cancer vaccines have entered phase 3 clinical trials, the possibility that we might one day be able to get our cancer shot together with our flu shot seems much more plausible."

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What if someday, instead of the usual “Flu Shots Today,” the cardboard sign in front of your local pharmacy read: “Cancer Shots Today?” Even if you were deathly afraid of needles, you would probably rush in to get an injection.

The idea that a simple inoculation could eradicate cancer might sound ludicrous. Sometimes however, when something seems too good to be true, it might actually turn out to be very true. Scientists have been working for decades to find the wonder jab that could thwart all cancers. That day has not yet arrived, but it may be drawing near.

Simply put, vaccines boost the immune system’s natural ability to protect the body against “foreign invaders,” such as bacteria, viruses or parasites. Traditional vaccines usually contain weakened versions of microbes that are able to stimulate a specific immune response.

When the immune system encounters these substances through vaccination, it responds to them and eliminates them from the body. The immune system also develops a memory of the invaders so that it will act quickly to protect the body against them in case of a future encounter.

In other words, the philosophy inspiring the science of immunology is like that old Chinese adage, “Give a man a fish and you feed him for a day. Teach a man to fish, and you feed him for a lifetime.” And this philosophy has been in play ever since 1796, when Edward Jenner inoculated an 8-year-old boy with pus from a cowpox blister in 1796 to protect the child against smallpox.

Prophylactic vaccines that prevent some cancers caused by infectious agents already exist. The US Food and Drug Administration (FDA) has approved vaccines against the hepatitis B virus that can cause liver cancer, and vaccines against the human papillomavirus types 16 and 18 that are responsible for about 70 percent of cervical cancers.

However, only one in six cancers worldwide are caused by preventable or treatable infections. Other cancers derive from genetic or lifestyle factors (tobacco use, diet, and physical activity, etc.), and/or environmental exposures to different types of chemicals or radiations. Therefore, cancer researchers are trying to develop a new generation of vaccines that could cure any cancer, including those that are not caused by an infectious agent.

The goal of the cancer vaccines in development is to enable the immune system to recognize cancer cells as foreign, or “non-self,” agents, rather than as harmless “self” agents. Foreign invaders such as viruses or bacteria have proteins on their outer surfaces called antigens that are not normally found in the human body. The adaptive immune system recognizes foreign antigens as “non-self” and proceeds to destroy them. By contrast, normal cells in the body have antigens that identify themselves as “self.” Self-antigens tell the immune system that these cells are not a threat and should not be attacked. Cancer cells carry both self-antigens and non-self, cancer-associated antigens. So they confuse the immune system with mixed signals.

A cancerous cell is a normal self-antigen-carrying cell gone wild. It divides, grows and proliferates uncontrollably. In a state of “madness,” the cancerous cell also starts to produce new non-self antigens that the immune system recognizes as a threat. But like a concerned parent faced with a teenager spinning out of control, the immune system resists the temptation to kick the troubled kid out of the house because it feels that its own once-sweet baby is still hiding in there. The immune system reacts, but weakly or inappropriately, and it does not manage to clear the body of cancer cells.

Therefore, the goal of a cancer vaccine is to overload the immune system with the information, “Bad antigen! Kill!” Many cancer vaccines send that message very well, but they do not always send the message long enough for the immune system to “remember” it. In some cases, the immune system recognizes the injected antigens as foreign and destroys them rapidly, before it can begin attacking the cancer cells efficiently. Without any further stimulation, the immune system can return to its normal (pre-vaccine) state of activity – i.e., it ignores cancer cells.

Therefore, Scientists have looked for a way to provide a steady supply of antigens. DNA vaccines may be the answer. DNA contains the genetic code for all the proteins a cell can make, including antigens. So scientists could easily synthetize in vitro pieces of DNA that contain the genetic instructions for any known cancer-associated antigens. This DNA could be injected alone into a patient as a “naked nucleic acid” vaccine, or inserted into a harmless virus.

If these vaccines performed as designed, the injected DNA would be taken up by cells that would begin to manufacture enough of the tumor-associated antigens to stimulate a very strong and enduring immune response.

The National Cancer Institute reports over 15 antigen-based cancer vaccines that were proven safe and effective on a small scale and are now being tested on a large number of patients in phase 3 clinical trials. Most of the new generation DNA-based vaccines are still in phase 1 or 2 trials. But they are progressing through the ranks. For example, PROSTVAC, a DNA vaccine against advanced prostate cancer developed by Bavarian Nordic has shown very encouraging results in phase 2 trials and patients are now being enrolled to start a large-scale phase 3 trial. Many DNA vaccines should soon follow PROSTVAC’s lead.

Vaccines represent a relatively new approach to fighting the spread of cancer. As a result, they have the potential to change the way we treat cancer worldwide and represent some of the most exciting new areas of medicine we’ve seen in a while. Now that they have entered phase 3 clinical trials, the possibility that we might one day be able to get our cancer shot together with our flu shot seems much more plausible.


Severine Kirchner
Penny Sleuth

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