MEDICAL BREAKTHROUGHS RESEARCH SUMMARY

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1 MEDICAL BREAKTHROUGHS RESEARCH SUMMARY TOPIC: Training the Body to Fight Melanoma REPORT: 3823 BACKGROUND: Melanoma is the most dangerous form of skin cancer that can be hard to treat and fatal if not caught in the early stages. Skin cancer is caused by rapid, significant amounts of ultraviolet radiation from the sun or a tanning bed that damages skin cells and causes them to create cancerous growths on the skin. These growths are called melanomas and can also develop from moles on the skin. Fortunately, if melanoma is caught early, it is almost always curable. Doctors recommend always doing a self-exam after being exposed to high amounts of UV rays. A simple self-exam consists of checking yourself all over for any possible lesions or unusual new moles or growths and determine if there is any change in existing moles or growths. (Source: TREATMENT: There are many treatment options for varying levels of melanoma such as surgery and chemotherapy. Surgeries for melanoma aren t always major procedures. There is also a simple excision; where the melanomas are removed along with some skin around the edges. For chemotherapy, success in melanoma cases has been limited. Dacarbazine is currently the only chemotherapy treatment that s been FDA approved to treat stage IV melanoma and is given as an intravenous infusion. (Source: NEW TECHNOLOGY: There may now be a better way to treat cases of melanoma. Immunotherapy is being tested on melanoma cases to see if doctors can turn a person s T cells into a weapon against skin cancer. T cells are the cells that carry out the function of the immune system. Immunotherapy uses medications to train a person s immune system to fight cancer cells and has so far shown promising results. T cells are first killed off in the body using chemotherapy and newly modified T cells are inserted. These new cells provide a more natural way for the body to fight melanoma. (Source: FOR MORE INFORMATION ON THIS REPORT, PLEASE CONTACT: Jim Ritter Media Relations Loyola University Medical Center If this story or any other Ivanhoe story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Marjorie Bekaert Thomas at

2 Michael Nishimura, Ph.D., Professor in the Department of Surgery and Associate Director of the Oncology Institute, Loyola Cardinal Bernardin Cancer Center, Loyola University in Chicago, School of Medicine. So tell me then about this gene therapy and how exactly it works. Dr. Nishimura: We isolate cells from a cancer patient and genetically modify them with specific genes which allow those immune cells to recognize the tumors. It gives them the specificity or reactivity and allows them to recognize targets on the cancer. And so for those at home, maybe that don t know the T-cells are fighter cells, can you clarify? Dr. Nishimura: Yes, they re white blood cells. They re part of your blood and when you get the flu; they become activated to fight flu virus infected cells and there are some in your body that can fight cancer cells. We actually engineer the cells to make them work better, so that they can target your cancer cells; which is harder to do naturally. Why the chemotherapy after you remove the cells and genetically alter them? Dr. Nishimura: There are two reasons for that. First, if you look at your blood, you have a normal level of white blood cells and when you deplete the white blood cells, there are signals which cause the ones that remain to grow and occupy the space. When we put these gene modified cells into somebody that s had the chemotherapy, the goal is for them to expand quite a bit in the patient so that they can go and fight the tumor. The second reason is there are many cells in your blood which can suppress the immune response against cancer. By depleting them first, we get rid of those negative cells; those cells that suppress, so we hope that the cells we put in expand and they function in a better environment. And then once those cells are in place, they re basically like a trained army and it s going to attack Dr. Nishimura: Basically that s correct. They are already genetically programmed to fight the cancer. How s that been working so far on the trial? Dr. Nishimura: I ve treated two patients; one unfortunately did not respond and one has a fairly nice clinical response. There s a number that we ve screened that weren t eligible for a variety of

3 reasons. They didn t meet the eligibility criteria, but there are also a lot of other therapies that are out there that compete for this trial. When did the trial start? Dr. Nishimura: About a year ago. Who would be best for this trial? Dr. Nishimura: The patient has to have advanced melanoma. Their tumors have to express the target that we re going after and the target is an enzyme which makes the pigment in melanoma. They have to have certain health characteristics. They can t have brain metastases. One of the patients that we screened turned out to have brain metastases and became ineligible. We don t want bleeding in the brain as a result of the therapy. So, there s a large entry criteria for it. You said this you re looking for a certain enzyme. Is it the most common? Dr. Nishimura: Yes it was surprising that this patient didn t have it in his tumor. Most of the melanomas express it. If the melanomas are black and most of them are, they express this protein. I was surprised. We came up with this from last year s work. Can you get more into the science of what you look for? Dr. Nishimura: There are specific proteins on the surface of a T-cell, a white blood cell, which tells it what targets to recognize. Again with the flu example, when you get the flu, you know the doctors look for swelling in your glands and in your underarms, you know? It s because your immune system is expanding and those cells that have the right proteins on the white blood cells which can recognize the flu are the ones that are expanding. So the idea is to take genes that encode those proteins from a cell that we know can target melanoma or any other cancer or virus for that matter, and transfer it to somebody else s cells. I could take your cells or anybody s cells and transfer that protein and that receptor will target the melanoma cells. That s how we do it. It s almost like using snake venom to make anti-venom, almost. Dr. Nishimura: Not quite, because it s more like taking the antibodies from a patient that is immune to the snake venom and transferring it to somebody else. We re basically engineering somebody s cells. In this case, this patient s cells with proteins that enable that cell to recognize the cancer. We re modifying their cells. How big of a breakthrough would you say this is then? Dr. Nishimura: Well there are a lot of trials that are out there doing this. We were the first ones to demonstrate that it was feasible in the laboratory, but Steven Rosenberg and others have done similar trials. This is new for Loyola. This is a new receptor. It s a new target and we re excited about it. We spent a lot of years developing this. We cloned this receptor almost 15 years ago and we ve done a lot of work to make sure that it s going to be safe. We already know

4 in animal models about the effectiveness and things like that. We want to make sure that we know as much as we could about this receptor before we ever put it into a patient. In some of the animal models, what were some of the stats? Dr. Nishimura: In some of our animal models, we can eliminate fairly large melanomas, both mass tumors and human tumor with T-cells that express this protein. Adoptive cell therapy is now becoming very exciting because this is a class of receptors like the chimeric antibody receptors out there, which have shown great promise in lymphomas. I think what it is now, is we re learning better how to use these cells; where before we weren t quite as knowledgeable about their biology and how to use them effectively in people. I think it s only going to get better in time and you can tell there is excitement because large pharmaceutical companies are starting to invest very heavily in this technology with a goal of commercializing these types of cells. Any idea how long a person would need to stay on this therapy before they start? Dr. Nishimura: In our trial, they get one single infusion; one single injection of cells. So the patient that you talked to, it was eight weeks ago and last time we checked which was a week or so ago, he still had three, four or five percent of the cells of his blood that were engineered cells and hopefully they will stay long term. The power of the immune system is its long term. When you are young; you get vaccinated for things, right? You don t have to get vaccinated again because your immune cells have memory that s different than chemotherapy. These cells potentially could be there for years. They could be there as long as he s alive; which we hope is going to be a long time. Was there anything to show how long life is prolonged, in the animal models? Dr. Nishimura: Well in animal models you can cure some mice with it. Mice live a year and a half to 2 years and months after there is no evidence of disease or of the tumor. In patient s it s hard to know what would happen to a patient if you don t treat them. My understanding was that when you re in stage IV melanoma was that you re pretty much at the end. Dr. Nishimura: In the old days that was true, but there are new therapies. There are new immune therapies that are showing great promise and that s one of the reasons it takes some time to enroll in experimental therapies. There are new FDA approved agents that have an impact on melanoma. They don t cure all of them and that s why we re still working to develop new therapies for this disease. This approach can work for other kinds of cancers as well. It doesn t have to be melanoma. We have other receptors that we re working with that we re headed toward putting into patients.

5 This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters. If you would like more information, please contact Michael Nishimura, Ph.D. Associate Director of Oncology Institute Professor of Surgery Loyola University Chicago Sign up for a free weekly on Medical Breakthroughs called First to Know by clicking here.