MD Anderson Cancer Center



[ Music ]>> Welcome to Cancer Newsline. A podcast series from the University of Texas MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention. Providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin, and today we'll be talking about B cell lymphoma. This is a disease that has been chosen as a cancer moon shot disease by MD Anderson. I have the co-leaders for the B cell lymphoma moon shot with me today. They are Dr. Michael Wong who is a professor in lymphoma and myeloma. And Dr. Richard Champlin who is the chair of the Stem Cell Transplantation and Cellular Therapy Department. All right, gentlemen, let's get the basics out of the way. Dr. Wong, somewhat B cell lymphoma?>> B cell lymphoma is basically the cancer of the lymphatic system. So everybody knows that our block circulation goes all over the body. In fact, there is another cellular circulation called the lymphatic system. It also goes all over our body. It is, it has lymphatic blood vessels and also has the origin of the system is the bone marrow. The circulation through the [inaudible]. And all the lymph node all over the body. Whether you can palpate in the superficial service or deep in our body. So they exist everywhere. So lymphoma is a disease, a cancer of the lymphatic system. You often find that lymphoma in the lymph nodes enlarge the [inaudible]. And the lymphoma moon shot is actually B cell lymphoma moon shot. Ninety five percent of all the lymphoma cases are B cell lymphomas.>> So B cell lymphoma we were talking a bit earlier. You said that actually out of most cancers, this is not a terrible one to have.>> Yes. Because lymphoma patients could survive for many years. And we actually are able to cure 30 percent of the patients. Let me also explain to everybody because lymphoma patient could survive for many years, therefore, the actual number of patients with lymphoma in America is actually a big number. Almost one million people live with lymphoma in America.>> Now when I was B cell lymphoma chosen? I know that after a while in certain patients it becomes resistant to treatment.>> So when you get the chemotherapy it, you know, kills the sensitive cells. But the resistant cells survive. And when they grow back, it's very hard to cure them. So we're looking to develop new treatment strategies. And in cancer there's really been a revolution in what we call new modalities of treatment. Historically we've used drugged just, you know, toxic drugs that kill dividing cells to kill cancers. Now we can target the fundamental genes that are causing the cancer to grow and specifically target those genes and not the genes that are in normal tissues and so called molecularly targeted therapy. So in our moon shot we have one project designed to find new and better targeted treatments that are what we call precision treatment for each patient's cancer. We've also found that the immune system can be activated to fight cancer better. And the immune system normally doesn't react very strongly against your own cancer because the immune system doesn't see it as different than the rest of our body. But through a new class of drug called Check Point Inhibitors, we can basically take the brakes off the immune system so it fights the cancer even better. And since we've shown that the cancer can be killed by immune cells, we now have a third category of treatment, cellular therapy. Where we actually manufacture immune cells that can specifically target and kill the cancer, and we can produce these cells in large numbers and then give them to the patient. So in our moon shot we have three major projects. One to look at each of these new, very promising modalities of treatment.>> Let's take just a slight step backwards. Do we know or can you identify people who are most likely to recur or relapse or become resistant to treatment? Do we know that, or is that part of the man shot?>> It's part of the moon shot. We, in the past we rely on the clinical features of the patients. How big the tumor, what's the proliferation rate, and how malignant it looks. But nowadays, we do genetic profiling. We know the genes, the driver genes. We know the mutations. We know, for example, there's the very famous saying called P fib three [phonetic] is actually protect us from cancer. But when the gene is, the good gene P fib three is a mutated thing, we found the tumor to be extremely resistant to cancer therapy.>> So you're hoping to kind of standardize treatment based on how people become resistant? I don't know if I'm asking that right.>> You are asking the right question, yes. That's what we are trying to do through manning translational studies especially molecular profiling, we want to see which tumors are resistant. Which tumor is particularly sensitive to which therapy. And we are rapidly coming to that point.>> Let's talk about the immunotherapy part. Obviously a lot of excitement generated about immunotherapy especially here at MD Anderson. We found a few checkpoint inhibitors that we've been able to exploit. What sort of targets do we have for immunotherapy? Obviously with melanoma and CTLA4, there are many other targets. Do we have a target for B cell lymphoma for immunotherapy?>> So the immunotherapy targets if you will are not really on the cancer, they're on the immune cells. So CTLA4 is a protein that is a natural regulator of the immune system that turns the immune system off so it doesn't overkill an infection if you will. And there's another one called PD1 that is a death signal to the lymphocytes. And so if we can basically take the brakes off the immune system when it would normally sort of turn itself off in responding to an infection. We don't want it to turn itself off when it's responding to cancer because it needs to maximally fight the cancer until the cancer is completely gone. So by effecting the regulation of the immune system, we can make it fight the cancer much more effectively.>> Are there other checkpoint inhibitors that we're looking at or are these two?>> Yeah, this is just the tip of the iceberg. And there's new ones, there's a very promising one called X40 and the whole family of these checkpoint inhibitors, you know, currently being investigated. So these are, these other ones are still in what we call preclinical studies. They aren't ready for human clinical trials yet. Although some including this X40 inhibitor is entering clinical trials now. So we hope to have those going in our program here within the next few years.>> And you said another arm of this moon shot is targeted therapies? Let's talk about target, because I think people get confused between a targeted therapy and an immunotherapy. So what sort of targeted therapies are we looking at, Dr. Wong?>> Target therapies usually that we aim, we target, we find the target either on the surface of the cancer cell or inside that cancer cell. And we design a small molecule drug and that specifically binds to this target and once the combination happens, the tumor dies. This is target therapy. In the past ten years, it has been the era of targeted therapies. Numerous targeted therapies has immerged. Some of the best examples like [inaudible]. [Inaudible] is a small molecule that target on the target in the blood cell called the target is called a.[ Inaudible ]Because it was discovered by General Burton [phonetic] in the 1950s in the Walter Reed army Hospital in Washington DC. Later on, we found that by inhibiting the targeting of this enzyme we can actually kill B cell lymphoma cells. And that those nowadays after you approve the pill based on the clinical trial that led by myself and my colleagues. And the drug is called [inaudible], and it can kill cell lymphoma cells.[ Inaudible ]And many lymphoma cells. Imagine in the past we have five drops of chemotherapy. We sometimes have to get the patient into the hospital to deliver this chemotherapy. This chemotherapy is.[ Inaudible ]Which means they cause low blood counts, they cause hair loss, and nausea, vomiting, the many side effects. But nowadays we have one pill, the patient swallows at home every day, and they actually do not have to be admitted to the hospital. They don't even lose hair. Their blood counts are never depressed. And the tumor shrinks at the same rate and maybe even better than the combination chemotherapies. So targeted therapies has meant the miracle killers, many miracles has caused by targeted therapies. So nowadays we are into the immunotherapy era while we continue to develop targeted therapies, we look to combine the targeted therapies with immunotherapies. Including antibodies, checkpoint inhibitors, and cellular therapies. And, above all, [inaudible] stem cell transplantation. We combine all those in a personalized manner to cure B cell lymphoma in each individual patient.>> So in each patient we look for the treatment that's the safest and simplest for the patient to receive. And we know that some patients can be cured with relatively and mild treatment that can be given just as a pill. Other people would have more aggressive lymphomas still need more aggressive treatment. And some even need a bone marrow transplant or a stem cell transplant to be cured. So our, one of our major goals is to be able to define just what each patient needs to have the safest and most effective treatment possible.>> How often do you have to do a stem cell transplant for B cell lymphoma?>> So typically we do an autologous stem cell transplant for B cell lymphoma if it relapses after a standard chemotherapy. So little more than half of the people would relapse with current treatments. And so those are the patients that typically receive stem cell transplants.>> And now that we're talking about stem cells, a third aim of the B cell lymphoma moon shot is cellular immune therapy. So let's talk about that. So, basically, you're engineering T cells or, you know, fighter cells in a lab, is that how it is?>> Right. So the immune system recognizes differences on their target cells that are not present on your normal cells. So the immune system is designed to fight viruses that attack the body. Now that lymphoma cells don't express what we call strong antigens, they don't notice much of an immune response. But now we can engineer the T cells or another kind of cell called the natural killer cell to specifically recognize proteins on the surface of the lymphoma. And so we've done this initially with the protein CD19. Which is present on all B cells and B cell lymphomas. And so we can engineer the T cells or the actual killer cells to specifically recognize the CD19 and kill those CD19 positive cells. Thus, they kill the lymphoma and don't damage normal cells in the body. So when using this strategy, a number of people. Or a large fraction of people who would have otherwise had fatal B cell malignancies, you know, can, in fact, be cured of their disease.>> How are you engineering these T cells? Are you, are they coming from cord blood, are they coming from the bone marrow? Or, you know, from the patient's own body? Where are they coming from?>> So right now we usually take the patient's own either T cells or MK cells and then introduce the gene that makes them produce the what we call a chimeric antigen receptor that binds to the CD19. That then redirects the cell to instead of binding a virus to binding the lymphoma. And then to kill the lymphoma. So through that engineering we've switched the immune system from fighting, you know, infectious disease to fighting cancer.>> It sounds like cellular immune therapy is an immerging field.>> It is. So this initial treatment with the CD19 specific T cells has been the first success with this type of therapy. But now we're looking to apply it as well an acute myeloid leukemia, to multiple myeloma, and to solid tumors. So there's new and very exciting studies and different forms of these chimeric energy receptor T cells or MK cells that can be used against a broad range of cancers. And we hope that our moon shot is going to lead the way for other cancers as well as just B cell lymphomas.>> And, Dr. Wong, you said that the goal for this moon shot is to increase the survival rate for B cell lymphoma to 60 percent which would be doubling it within five to ten years. In my mind I'm thinking a 30 percent survival rate isn't all that great. Even for a disease that seems to be not as serious as others.>> I totally agree. The 30 percent cure in the past cancer equals the deaths. And the 30 percent is a major forward, is certainly, it is certainly not adequate. And that's why we aspire for better goals to double the cure rate. And we think this is the time that many technologies of science has come together with the collaboration in the patients, communities, industrial centers, academic centers, government. This is the, we have the unprecedented chance to do this. And there's no better place to do this other than MD Anderson.>> So where, how is the survival, is this happening for people with acute disease? People with relapsed disease or recurrent disease? Why are we only at 30 percent?>> Some of the patient when they are cured they respond to therapy, the cancer never come back. The majority of the cases the cancer keep coming back. After the first line of therapy then we give them a second line of therapy. They responded [inaudible] then they come back again. The third line, fourth line, fifth line, seventh line. At one time I gave one patient 15 lines for therapy. But good that we are able to convert the acutely deadly disease into a chronic disease. But the ugly side is that the tumor become more resistant each time and the interval is shorter each time. Eventually after many, many lines of therapy, it is so resistant it stop responding to therapy as well. And it caused the mortality. And that's the big part of the moon shot is to find ways to mechanize from the why this resistance appears and how to actually combat, overcome the resistance. Therefore, we can cure the disease.>> And so the cancer, you know, unfortunately, can find other pathways to make it grow. So if we block one pathway, that may kill a large fraction of the cancer but often there's a small fraction that survives and then can grow back. In the same way, there is what we call immune escape mechanisms where the tumor can block the immune system from killing it. So even though we've made major advances and a large fraction of people now can be cured, we have to overcome these mechanisms of resistance to cure everybody. So this is an ongoing effort. We made great progress, but there's still a lot of work to be done.>> And I understand that B cell lymphomas because a fair amount of cancers, you know, are typically in people 50 and older. Now this is a disease that has a more wide ranging demographic, does it not?>> Yes. So the cancer areas are most common in older individuals. But lymphomas can occur in people of all ages. And so there's some children with lymphoma. But the average age is in the 60s for B cell lymphomas.>> And for some patients especially young patients, the Hodgkin's lymphoma and the majority of the patients in the 20s or a little younger or older. So the Hodgkin's lymphoma is mainly a disease of the young people. And there is a second peak [phonetic] but a second peak is not as popular as the first peak in the young people.>> Well, it sounds like you both have very promising avenues to work on for this moon shot.>> Yeah, and so we're very excited about the opportunities. And, you know, we're, you know, it's great to be here at MD Anderson where we have both the support of the moon shot program. We have large numbers of patients that are in need of better treatment. And we have the opportunities to do clinical trials to prove that the innovative treatments, in fact, will be better.>> Similar to landing a human, in the moon shot program is a collaboration of many people. Many technologies combined. So moon shot is a moon shot involving many faculties from different departments. And many technologies in the different platforms. So we think that there are some vast resources and talents at MD Anderson. And we are going to work as a team.>> Thank you both for being with me. If you have questions about anything you've heard today on Cancer Newsline, contact ask MD Anderson at 1 877 MDA 6789. Or online at ask. Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.[ Music ] ................
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