The Iconoclast: The Rise of Immunotherapy
I am by no means an expert or doctor, but cancer and molecular biology are my two favorite areas of science. So I read papers, listen to lectures, and study textbooks in these fields. Though I have an incredible amount left to learn, I definitely have accumulated some knowledge and opinions over the years. With that caveat, I’ve decided to write a four part series (it will be posted every Sunday) describing what I believe the future of cancer treatment will look like. Most of what I say will be speculation (duh), but it will be based on facts and current research trends. So, here we go…
“Immunotherapy, the use of the immune system to attack a patient’s cancer, will rise to the level of surgery, chemotherapy, and radiation as a fourth major treatment strategy for cancer.” Current cancer therapies include the use of surgery to remove tumors and the use of either chemicals (chemotherapy) or radiation to kill neoplastic (cancerous) cells. However, immunotherapy will harness the cells of the body’s immune system, and get them to recognize cancer cells as foreign, and eventually destroy them.
First, what evidence do scientists have that the immune system can kill cancer cells? After all, if the immune system could recognize and kill cancer cells, wouldn’t cancer patients eventually fight off their cancer, just as people regularly fight off and recover from the flu? Though this is a valid question, and its answers have hindered the development of immunotherapy as of yet, there is strong evidence that the immune system can recognize and kill cancer cells to some extent. Amplifying this ability will form the core of immunotherapy.
The first piece of evidence that the immune system can fight cancer comes from a depressing statistic: people who have received organ transplants are significantly more likely to get cancer than members of the normal population. How significantly? It varies for different cancer types, but we are not talking about small numbers. People who have received transplants are 14.3 times as likely to get thyroid/endocrine cancers, 13.8 times as likely to get some form of mouth cancer, 10.3 times as likely to get Non-Hodgkin’s lymphoma, 9.1 times as likely to get kidney cancer, and 5.5 times as likely to get bladder cancer. The incidence is dramatically increased in other cancers as well. (Source: The Biology of Cancer by Robert A. Weinberg, page 680). Why is this the case? As it turns out, most patients who receive organ transplants must take immunosuppressant drugs in order to keep their immune system from attacking their new organ. The thinking is that, since a suppressed immune system seems to correlate with an increased risk of cancer, then the immune system probably plays some role in preventing cancer development. The same increased cancer risk is found in AIDS patients. Correlation does not ensure causation, but such strong correlation is extremely suggestive. There have also been many experiments in mice that show that a reduced immune system makes them more easily develop cancer.
So what exactly is immunotherapy? Immunotherapy currently comes in three main forms:
1. Cancer vaccines. See this previous Iconoclast interview for an explanation: http://theiconoclast.info/?p=102.
2. Passive immunization. Passive immunization consists of injecting a patient with an antibody to their cancer cells. Certain neoplastic cells have an abnormal pattern of antigens on their surface. Abnormal antigens may be present, or normal antigens may be present in increased numbers. Passive immunization consists of injecting an antibody to such an antigen, thus causing the antibody to bind the cancer cell and (1) prevent it from growing and replicating and/or (2) target it for destruction.
3. Bone marrow transplantation. The immune system is generated by cells in the bone marrow. A common treatment for many hematological cancers, such as leukemia, is to give patients what is known as a bone marrow transplant. This usually results in a cure. In a bone marrow transplant, the patient’s own immune system is either partially or completely eradicated (using drugs and radiation). They are then given new bone marrow from a completely different person (known as a donor). This bone marrow then regenerates the immune system, and the patient ends up with a replica of the donor’s cancer free immune system.
The original intent of bone marrow transplantation was to cure cancer by simply replacing the cancerous immune system with a noncancerous one. However, though cures were being achieved, scientists soon realized that the cures were not entirely a result of simply “replacing the bad with the good”. There was a much more exciting phenomenon going on…
The graft versus tumor effect. As it turned out, some cancer cells still remained inside the body after the attempts to destroy the immune system. However, the newly generated immune system of the donor recognizes these cells and destroys them. This results in a long term cure. Though the graft versus tumor effect does not cure solid tumors (large tumor masses create an environment near them that renders many killing cells of the immune system useless), research is currently underway to understand exactly why this is, in hopes that one day the graft versus tumor effect may be used to treat solid cancers.
So, has immunotherapy been tried yet in humans? Has it been successful? The answer to both questions is yes. Passive immunization is already in clinical use. The vaccine Herceptin is being used to treat some forms of breast cancer, specifically those that over-express the HER-2 antigen. Many more passive immunization procedures are being investigated. The other type of cancer vaccine, the kind described in the interview with Dr. Parcells that relies on immunostimulatory molecules, is currently in clinical trials for a variety of cancers. And finally, researchers have begun to report preliminary evidence (just a few case studies) in which bone marrow transplants have caused remission in solid cancers (breast and ovarian so far). Though there is much work left to do, and still huge obstacles to overcome, I believe that one day immunotherapy will be a common and effective type of cancer treatment.
Brad Rybinski
Sources:
· The Biology of Cancer by Robert A. Weinberg
· http://www.herceptin.com/pdf/AdjuvantCorePatientBrochure-NEW.pdf
· http://cancerres.aacrjournals.org/cgi/content/full/68/8/2561
· http://www.ncbi.nlm.nih.gov/pubmed/12531922
· http://jco.ascopubs.org/cgi/content/full/22/19/3846
· http://annonc.oxfordjournals.org/cgi/content/full/18/10/1751
· http://www.nature.com/bmt/journal/v25/n6/full/1702206a.html
· http://www.centocor.com/centocor/images/immunology.jpg
