Treatment Update: Gene Therapy with Charles Link, MD, FACP

By Charles J. Link
WebMD Live Events Transcript

Charles Link, MD, FACP discusses the mechanism, use and future of gene therapy for cancer treatment.

The opinions expressed herein are the guests' alone and have not been reviewed by a WebMD physician. If you have questions about your health, you should consult your personal physician. This event is meant for informational purposes only.

Moderator: What exactly is gene therapy? How does it work?

Dr. Link: Gene therapy is a field where a piece of genetic information is transferred into a cell. The cell then uses the gene to produce a product that treats a disease such as cancer. The usual method to deliver a gene into a cell uses an artificial virus to move the gene. This is how a cold virus, for example, expresses genes in us when an infection occurs. The difference is that in this setting the virus used to deliver the gene cannot replicate or cause an infection.

Moderator: As everyone is probably aware, human gene therapy has been under a great deal of scrutiny lately. What is the research community doing as result?

Dr. Link: The community fells strongly that the types of therapy under development will be important for the future of medicine and that, like all new technology, careful attention to detail is required to move the field forward.

Moderator: How do you "program" the virus to perform the correct task?

Dr. Link: There are several different things that can be done to "program" a virus. It can be designed so that it is only active in a specific type of cell or tissue in the body. It can be designed to enter only a specific cell in the body, or drugs can be used to turn the gene on and off when you want it on or off.  It can be used in several ways depending on the disease situation. In the case of a genetic disease where a gene abnormality exists that leads to disease, knowing the gene can be used to construct a virus with a repaired version of the gene. In this case, the virus then delivers a correct copy of the gene to fix the broken gene (mutated). In the case of cancer, genetic information can allow a scientist to develop a new strategy to kill the cancer cell through its soft spot, meaning how it is different form a normal cell.

Moderator: Is gene therapy designed as a cure or just a way to treat symptoms?

Dr. Link: It depends on the situation, it has been used for both. 

Moderator: What is it in terms of cancer?

Dr. Link: Some cancer trials have been aimed at trying to cure cancer patients, but most have been designed to reduce the amount of cancer in someone to help them but not cure them.

Moderator: Can gene therapy change inherited traits?

Dr. Link: No, current gene therapy trials are designed to fix tissues in the body (so called somatic gene therapy) and not to change any inherited genes (germ cells). Since the ovary and testes are not ... genetically changed, the offspring are not affected. This is actually an important safety concern. Researchers go to great efforts to make sure that the germ line (ovary or testes) is not affected. I think that once someone truly understands what a gene does and has established its level, say in cancer cell compared to a normal cell, it's OK to patent it. This leads to investment that allows drugs to be developed. However, a gene sequence alone that has not been shown to have an effect or difference between a normal and cancer cell, for example, should not be patented or a least not patented for any way it might be used in the future. 

The testes are the source of the genetic material from the male that mixes with the egg from the ovary of the female. Therefore, if new genes were transferred to the testes there would be a risk of having an inherited new gene in a child conceived from that sperm.  I wanted to add that in the United States no experiments have ever been considered to change the inheritance of future generations. The gene therapy starts and stops within each individual patient. There are a number of different viruses that are being explored to use as gene delivery vehicles. In any given situation you need to use the right tool for the job. Some viruses do transient gene transfer, while others change things long term. 

Moderator: Are there side effects to gene therapy being used a cancer treatment?

Dr. Link: As an oncologist, I have never seen a therapy for cancer without side effects and gene therapy is no exception. People in the field do believe thus far that gene therapy has far fewer side effects than, say, chemotherapy. But the track record and effectiveness of chemotherapy is far superior. Gene therapy is in its infancy as a field. But we expect it will lead to major advances in  many diseases, including cancer. 

Moderator: Have there been promising studies done regarding gene therapy's treatment of cancer?

Dr. Link: Yes, several. For a number of different cancers and leukemia, gene therapy has been used and patients have had evidence of cancer regression. Theses initial results are encouraging and  parallel the types of responses first seen with a number of other types of drugs that are now standard treatment in the US.  In our trials in patients with ovarian cancer, we have seen patients with tumors that have gotten smaller or are no longer visible by x-ray studies.

Moderator: There were promising gene therapy research results announced by French researchers. Can you tell us a bit about that?

Dr. Link: Yes, it is actually a very exciting development. Two infants with the "bubble boy disease" were treated by putting fixed versions of their defective (broken) genes into them. As the children grew, their immune systems regenerated and they became normal or near normal. If the effects last, this is a very major breakthrough in  the field. 

Moderator: Can gene therapy be used in conjunction with chemotherapy?

Dr. Link: Yes, in fact a trial conducted at the MD Anderson Cancer Center has shown very nice results in  patients with head and neck cancer who were given gene therapy with chemotherapy. I think more clinical  scientists will attempt such combinations based on these results.  I suspect that sometime in the next three to five years the first gene therapy will be approved for use in the U.S., probably as treatment for patients with incurable cancer. 

Moderator: Do you see this vehicle being used as preventative medicine in the future?

Dr. Link: Yes, I do. in some situations such as inherited cancer, broken (mutated) genes have been shown to cause an extremely high rate of cancer in the families. In this situation, it will be logical in the future to transplant corrected genes to prevent cancer. At this time, however, this is too technically complex to be doable. 

Moderator: Let's look at the patient's perspective. How can a cancer patient find and join a gene therapy clinical trial and who is right for such a trial?

Dr. Link: The best source of information on clinical trials for cancer is the National Cancer Institute in Bethesda Maryland.  They maintain a database of available trials, not just for gene therapy, but for any new cancer treatment. A patient's doctor can get to this information through a PDQ database (Physician Data Query). This database lists many of the available studies underway. Gene therapy is not currently conducted in the US outside of an experimental setting. 

Moderator: Do gene therapy trials hold any more risk for the patient than other trials?

Dr. Link: In my opinion, gene therapy trials for cancer have show much less risk than trials using chemotherapy where life threatening side effects are common. However, as with all experimental therapy, there may be risks we have not yet observed in patients, since a relatively small number have been treated. Of course, decisions to participate in such trials are balanced against the risk from the disease. In  the case of cancer, the vast majority of patients had already failed all known therapy and are considered incurable by any conventional approach (chemotherapy, surgery or radiation therapy).

Moderator: From the patient point of view, what should a cancer patient considering  a gene therapy trial keep in mind?

Dr. Link: I think they need to understand that the track record for new experimental therapy is thin. They need to ask direct questions to the investigator of what expected side effects have been seen in humans or even in animals when the gene therapy was used. They should find out what parts of the trial are their financial responsibility (if any) and they need to find out how long they will have to be at or near the treatment center. You should always ask for the latest information about how effective the treatment has been in any patients already treated on the protocol. 

Moderator: Well, our time is about up. Dr. Link, do you have any parting comments?

Dr. Link: I think the online community tonight has asked very good questions and please keep open hope for this new and exciting field. Thank you, Dan. Goodnight all.

Moderator: Thank you for your time this evening. It has been extremely informative! Our guest this evening has been Dr. Charles Link, Director of the Human Gene Therapy Research Institute. Good evening.

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