Dr. Christine Lu-Emerson (Guest): Sure. Thank you for having me on the show. So, Glioblastoma Multiform-A is a Grade IV primary brain cancer. What this means is that this is a cancer that arises from the brain cells in our brain. So, unlike other cancers we might have heard of, this didn't spread from any other part of the body. This came from the cells in the brain itself. Unfortunately, it is a very aggressive type of cancer and, despite aggressive treatment, which often includes surgery, radiation, and chemotherapy, the survival is just not as good as we would like it to be.
Melanie: So then, what's going on in the world of immunotherapy as it might start to relate to glioblastoma?
Dr. Lu-Emerson: Sure. So there's been a long history in the oncology world of looking into harnessing our own immune system in terms of attacking the tumor. It sort of makes sense because our immune system is geared up to innately recognize things that don't belong in our body, which should include tumors, and hopefully attack it, keeping us healthy. One of the big questions is, “Well, why are cancers allowed to survive in patients and why isn't our immune system doing much about it?” And so, a lot of the research done in oncology is trying to understand how cancers will bypass the immune surveillance that's going on. And in glioblastoma, what's very interesting is the tumor is, so to speak, very smart. It has figured out a way to not only directly suppress our immune system by deactivating the natural lymphocytes, our usual active immune cells in our brains, to not work, but it also increases the amount of immune cells that keeps our immune system quiet. So, in essence, the glioblastoma tumor turns off our immune system and that allows it to grow unchecked.
Melanie: So, as I understand it, Dr. Lu-Emerson, T cells are our little fighters, our little armies, and they’ve got blinders on when it comes to some cancerous tumors?
Dr. Lu-Emerson: Exactly.
Melanie: So, you're working with them, right? To get them to learn that these are enemies, as it were. Now, explain to the listeners how you do that.
Dr. Lu-Emerson: Well, I'm not an immunologist but I will try to explain it the best way I understand. Basically, what we do is we help our immune system along. So, we basically will take part of the patient's tumor and mix it up with cells that are normally found in our body and these cells, when they're mixed with these tumor parts, what they do is they present these tumor parts in a way to activate the immune system. So, even though the tumor has turned it off, we are bypassing that off mechanism by helping it-- by presenting these tumor parts to the immune system and thereby activating it another way.
Melanie: Very good explanation.
Dr. Lu-Emerson: So, what ends up happening is these patients who are enrolled in our trial, they all have to undergo a second surgery. Now, this is not unusual; oftentimes with patients, if surgery is feasible, we do advise them to undergo a second surgery. The advantage of this is one, it helps get rid of tumor cells that have grown back. Two, it also ensures that this is truly tumor cells that are growing back, not just some scar tissue that looks like tumor cells. So, after the surgery is done, we basically will take parts of the tumor tissue that we have collected and we mix it in with what we call "heat shock protein". Now, this is a protein that is found everywhere in our body and it's responsible for helping to turn on and off the immune system. So, by mixing these tumor parts with this heat shock protein, we're able to make a vaccine that we just inject like any other vaccine in the patient's arm and we're able to stimulate our immune cells to recognize the tumor.
Dr. Lu-Emerson: The study is randomized, so I do caution patients that they are not guaranteed and as much as I would love for all patients to try it, for a good study, we need to have a control arm, because we just don't know if this is going to work or not. So, basically, there are three arms to this study. Two out of the three arms will get the vaccine and a third arm gets standard of care which is a type of targeted drug named bevacizumab, or Avastin. That is standard. So, I do warn my patients when they're interested in this that I cannot promise you that you will get the vaccine but the odds are good that you will be one of the two arms that does get the vaccine.
Melanie: So then, tell us, is this a national study?
Dr. Lu-Emerson: Yes. This is a study that's done around the country with various institutions participating in it. As you probably know, brain tumor is just not as common as some other cancers like lung, or breast, so in order to get a good study going, we need enough patients and one center alone is not going to be enough to generate enough data for us to really know if this is going to work or not. So, this is the study that is open across the country at multiple neuro-oncology centers.
Melanie: And, what's the certain criteria that patients must meet to be involved?
Dr. Lu-Emerson: Good question, Melanie. So, basically, these patients have to have confirmed recurrent glioblastoma. In other words, when they go for their surgery, we must see that this is tumor cells coming back, not just scar tissue. Not only that, these patients who are enrolled have to have at least 90% of their current tumor resected. So, just doing a biopsy is not enough. We need enough tissue to make the vaccine. It requires a lot of tumor tissue to make it--about 5 grams. It is a little stringent in terms of inclusion criteria, but I'm hopeful that we'll be able to find some patients to meet that and enroll them in this trial.
Melanie: What else would you like them to know about what's on the horizon about immunotherapy and T Cells and glioblastoma?
Dr. Lu-Emerson: Sure. I think vaccine therapy is just one way of using our immune system to fight these cancer cells. Another thing that has come out that people might have read in the news are something called “checkpoint inhibitors”. So, as I said, the tumor is very smart in that it figured out how to turn off our immune system and one way of doing it is that it signals, via a very specific pathway, to our immune system to basically being in off position. Well, drug companies have found and developed multiple medications that actually blocks that mechanism. So, this is actually being used in other solid tumors such as lung cancer, melanoma, GI cancers and we're using these drugs called checkpoint inhibitors to basically unblock the off switch, so to speak, that's been activated by the cancer cells. So, I'm hopeful that this will also come into the field of neuro-oncology and we'll be seeing this more in the use of glioblastoma.
Melanie: Absolutely fascinating, Dr. Lu-Emerson. Tell us about your team at Maine Medical Partners.
Dr. Lu-Emerson: So, we have a fantastic neuro-oncology team. We have a great set of neurosurgeons who are very experienced with respecting tumors and understanding the type of delicacy that's needed to respect a tumor from a patient's brain while leaving them as intact as possible. We have a whole cadre of medical oncologists who are quite knowledgeable about these brain tumors and provide an excellent system in terms of supporting the patient through chemotherapy. Of course, we can't forget our radiation oncologists who provide a key portion of the standard treatments that we use. In addition to that, we have a neuro-navigation system. As you can understand, navigating the world of cancer is very frightening for patients. Not only are you dealing with the struggle of "Hey, I’ve got something serious going on in my body," there are a lot of different doctors, a lot of different appointments that are made, and they neuro-navigators are nurses that help the patients navigate the system. Who are their doctors? Why do they have many different doctors? So, they are just as crucial to our team as the doctors, themselves.
Melanie: Wow. Thank you so much. What great information, Dr. Lu-Emerson. Thanks for being with us today. You're listening to MMC Radio and if you have more questions or want more information about the glioblastoma clinical trial, you can go to mmc.org. That's mmc.org. This is Melanie Cole. Thanks so much for listening.