As researchers find new genes involved in the development of cancer, the possibilities for gene therapy continue to grow. Of course, in order to treat someone using gene therapy, doctors have to know which genes are altered or missing. While our knowledge of gene mutations involved in cancer continues to expand, our ability to detect these changes in individuals is still fairly basic. But research in this area continues at a rapid pace.

Techniques for Getting Genes Into Cells

So far, the biggest obstacle to gene therapy has been the ability to get genes into cells. There are 2 main techniques (in vivo and ex vivo) for doing this.

In Vivo Techniques

One approach is to somehow put copies of the gene directly into the body, where they will be taken up by the cells you want to target. These are known as in vivo (within the body) techniques. One of the problems with these techniques is that they might require injecting the genes directly into the tumor(s) to have an effect. This could be a problem for hard to reach tumors or in cases where the cancer may have already spread to different parts of the body.

Ex Vivo Techniques

Another approach is to take some of the targeted cells out of the body, add the needed gene(s) to them in the lab, and then place them back into the body. This is known as an ex vivo (outside of the body) approach.

This is more likely to be useful for activating the immune system to fight the cancer. For example, immune system cells might be taken out of the body (from the blood or bone marrow), given genes in the lab to help them find and kill the cancer cells, and then infused back. Or, cancer cells could be removed by surgery, treated in the lab to make them more likely to provoke an immune response, and then given back into the body. The immune system would then attack these cancer cells and other similar cells in the body.

Vectors to Get Genes into Cells

Genes, which are small strands of DNA, are not easily inserted into cells. Just injecting many copies of a gene into the body (such as into the bloodstream) isn't likely to be helpful, as the DNA would be destroyed before it ever got into the cells.

Therefore, researchers are studying different types of vectors (carriers) that can be used to help get genes into the target cells.

Viruses

We normally think of viruses as germs that cause infections. But viruses have some special properties that make them useful tools in gene therapy. Viruses reproduce by "hijacking" infected cells - they inject their genes (in the form of DNA or RNA) into the cells they infect, which causes the cells to make the protein parts for more viruses. Many viruses attack only certain kinds of cells, which means it might be possible to direct them at specific types of tumors.

Gene therapy researchers try to use only viruses that might be well-suited for the task. They use viruses that are fairly stable and aren't likely to cause disease. In the lab, the needed gene is put into the virus, and any harmful viral genes are removed. The virus is then given to the patient (via either an in vivo or ex vivo technique) to "infect" the cancer cells, and the gene is passed on to these cells. Viruses seem to be the most efficient vector for getting genes into cells.

But there are some possible problems with using viruses in gene therapy. Viruses may trigger an unwanted reaction by the body’s immune system, which could make the treatment ineffective (especially after the first round of therapy) or even lead to more serious health problems such as autoimmune reactions. Another concern is that researchers can’t always control exactly where the viral gene might be inserted into the cell’s DNA. It could possibly insert itself into the middle of one of the cell’s functioning genes, leading to an unwanted mutation.

Liposomes

Another strategy is to try to put a copy of the gene into the cells using liposomes, which are tiny fat bubbles. In the lab, the bubbles are created around plasmids, which are small, circular pieces of DNA. Once injected into the body, the liposomes can fuse with cell membranes, emptying their plasmid DNA contents into the cells.

Using liposomes as a vector has some advantages and disadvantages when compared to using viruses.

This method is less likely to provoke an immune response and may cut down on the chances that the patient will become sick from the treatment. Liposomes can also hold larger amounts of DNA than viruses, which means they may be better suited for carrying larger genes. Finally, liposomes can be modified by changing the contents of the fats, proteins, or other molecules that make up the bubble. This may be helpful in targeting them at specific types of cells in the body.

But liposomes may be less effective than using viruses, because the DNA is less likely to end up inside the cells. And because the liposome-DNA complex has to be injected directly into the tumor itself, it may be limited as to what kinds of cancers it can be used for.

Cells Targeted in Gene Therapy

Researchers have focused on 2 major targets in cancer gene therapy: the tumor cells themselves and immune system cells that might be induced to attack the tumors.

Tumor Cells

Tumor cells are the obvious target for gene therapy. Using either in vivo or ex vivo techniques, gene therapy is being studied as a way to cause tumor cells to die (or at least stop growing rapidly). It may also be used to add genes to make the cells more visible to the immune system or more sensitive to chemotherapy, radiation therapy, or other treatments.

Immune System Cells

Several types of immune system cells may be useful in gene therapy. For example, special immune cells called dendritic cells seem to be very important in helping the immune system to attack cancer. They can be removed from the body and then altered in the lab to make them more likely to attack cancer cells once they are put back into the body. Studies involving dendritic cell cancer "vaccines" are among the furthest along in terms of gene therapy development.

Related Forms of Therapy

Other gene-based forms of therapy are also under study. Instead of directly affecting the genes themselves, these approaches affect the cells' ability to turn genes into proteins. They work by attacking messenger RNA (mRNA), which is the intermediate step between a gene and its protein.

For example, scientists are now trying to use mirror images of faulty genetic material (called antisense DNA or RNA). These substances bind to specific mRNAs, which basically stops the gene from making its protein.

A newly discovered type of RNA (known as small interfering RNA, or siRNA), may also be useful in preventing genes from being translated into proteins.

Again, the main problem with these approaches may be getting these small molecules into the target cells. Research in this area is under way.

Revised: 05/24/2007