Monday, November 19, 2007

Cancer Vaccines, or Getting the Immune System to do what Chemo Can’t

Tumor vaccines are one of the hottest topics in cancer research these days. Most people think of vaccines as something we give to children to keep them from getting infections – and in the spirit of flu shot season - I am going to discuss the different types of tumor vaccines and whether they show any promise yet.

The simplest definition of a vaccine is that it is something injected into the body that stimulates an immune response. The flu shot, for example, is an injection of proteins that come from the influenza virus. These proteins will stimulate your immune system to respond to the virus that causes influenza and hopefully kill the virus before it makes you sick.

The idea behind a tumor vaccine is slightly different. Since the patient already has cancer, the purpose isn’t to prevent cancer (the way a flu shot prevents flu), but rather to strengthen the immune system to do what chemotherapy often cannot: kill the last few cancer cells and keep the disease from ever coming back.

There are several types of tumor vaccines. The two most common types are peptide vaccines and dendritic cell vaccines.

A peptide vaccine is most like the flu shot – a patient is injected with a piece of a protein that comes from a cancer cell in the hopes that this will trigger the immune system to respond to the protein and kill whatever cells (cancer cells in this case) have the protein. The major benefit of this approach is that patients rarely have a bad reaction to being injected with a small piece of a protein, so the side effects are minimal.

Unfortunately, the two main problems with the peptide vaccine are:
1. Not everyone is capable of reacting to every peptide
2. The patient’s immune system has to be relatively intact in order to process the peptide and respond appropriately.

Patients being treated for cancer often have very weak immune systems because of chemotherapy, making this a major limitation for peptide vaccines.

Peptide vaccines are being developed for many types of cancers, and early reports of success are already being published. In fact, one of my patients was treated on a peptide vaccine trial before coming to me for my clinical trial. Unfortunately, the vaccine was ineffective in his case.

A dendritic cell vaccine, in contrast, involves taking immune system cells from the patient, putting the piece of protein that is being targeted by the vaccine into these cells in the lab, and then injecting the manipulated cells into the patient. In theory, this method is more efficient and requires less of a functional immune system to work. The difficulty lies in successfully manipulating the cells in the lab, a process that has not been perfected yet. There are a number of reasons why dendritic cell vaccines are more likely than peptide vaccines to work in the long run, however. I am proud to be an associate investigator on a clinical trial that is about to open at the NIH involving the development of a dendritic cell vaccine for patients with leukemia who have undergone a bone marrow transplant. (As soon as the trial is open, I’ll talk more about it and include a link to the website that contains a full description.)

A problem common to both vaccine strategies is figuring out what cancer cell proteins to use as a target. Interestingly, a gene known as WT1 that my laboratory has been studying for a number of years, appears to make a protein that is a prime candidate to be the target of a cancer vaccine. WT1 is found on many types of cancer and it may play an important role in the life of the cancer cell. Because it is found on very few non-cancer cells, normal cells are unlikely to be mistakenly attacked by the immune system, causing harmful side effects. Several cancer vaccine trials are ongoing using WT1 as a target, including this one and this one.

In summary, cancer vaccines are very promising because they should allow oncologists to utilize the patient’s own immune system to treat his or her cancer. As the immune system is usually very specific about what it attacks, cancer vaccines will make unwanted side effects far less likely than with traditional chemotherapy. Unfortunately, the field of cancer vaccines is still in its infancy, and much work remains before they become a routine part of cancer treatment. Hopefully, we and others will be able to make this a reality in the near future.

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