Thomas Marron, MD, PhD, thoracic medical oncologist at Tisch Cancer Institute at Icahn School of Medicine at Mount Sinai, talks about developing a personalized cancer vaccine.
For our viewers who may have heard cancer vaccine, can you explain what it is that you’re looking at? What is a cancer vaccine?
MARRON: Sure. So a cancer vaccine is exactly what it sounds like. Just as with the COVID vaccine—where we’re teaching your immune system how to recognize COVID so that it can patrol your body and, when it sees COVID, quickly eliminate it—cancer vaccines try to teach your immune system how to recognize your cancer as something foreign and eliminate it. Your immune system is really there to differentiate between foreign and self, as you want your immune system to attack coronavirus, but you don’t want it to attack your skin. Your cancer is somewhere in between those because you were not born with cancer, so it is foreign to your body, but cancer has a variety of ways of hijacking your immune system and turning your immune system off and keeping your immune system from recognizing it. We have a variety of different types of cancer vaccines, and all of them are really geared towards teaching your immune system to recognize your cancer as the foreign thing and kill it; some of these trials are geared at helping the immune system kill large or metastatic tumors tumors, but some trials, such as in this trial we recently presented, are for patients who may only have microscopic metastatic disease, meaning tiny little bits of disease elsewhere in the body that remain after a patient undergoes surgery or radiation. In this setting, the aim of a vaccine is to enable your immune system to circulate throughout your body and identify those spots and eliminate them.
How do you put a cancer vaccine together? Is it a form of immunotherapy? Is it personalized per patient?
MARRON: Immunotherapy’s kind of an umbrella term for any sort of cancer therapy that uses the immune system to do its dirty work, or our dirty work for us. Cancer vaccines can be personalized or they can be general vaccines that can be given to anyone, and we have a variety of different approaches. Sometimes we inject things into the tumor to turn the tumor into a vaccine. Those are called in situ vaccines. In the case of this vaccine we recently presented, it’s a personalized vaccine that is given to patients who have had their tumors removed, but whom have a high chance of the cancer coming back due to residual disease. What we do is we take a patient’s cancer and we take some blood from them to study what is unique, or different, about their cancer compared to their normal cells. We use a computational pipeline, which is a computer program that can predict 1) what is it about our cancer that is most foreign? 2) What is it about our cancer that is most easily targeted by a patient’s unique immune system? And 3) what is it that we should be using to teach our immune system to recognize? Using this program we can predict what would be the optimal components of a vaccine, and we synthesize synthetic versions of the cancer-specific proteins.
For this particular vaccine that you have in trial, are there certain cancers that it works better with or that it’s geared toward?
MARRON: So this trial was for patients who have a very high likelihood of recurrence after curative intent therapy, which means that these are patients that have undergone surgery or, in the case of multiple myeloma, they’ve undergone autologous bone marrow transplant. And at the time when we start the trial, they don’t have any obvious evidence of disease in their body, but we know that these patients had at least a 30 percent chance of the cancer coming back based on historical data from their specific stage of their cancer or the type of cancer they had. We wanted to look at this population to see if we could vaccinate these patients to hopefully train their immune system to recognize the cancer. In the end, the goal is both to keep the cancer from coming back and also, if the cancer does come back, to make sure that their immune system is primed so that, if we give them a subsequent line of therapy, they’re more likely to respond. We aim to prolong what we call progression-free survival, which is the time between when they have their treatment and when the cancer comes back, but our overall goal is always to increase overall survival, meaning increase lifespan.
In this particular trial what phase are you in? I’m assuming this, because it’s an agent, it is in stages or phases. And how many patients over what period of time?
MARRON: So this was a brand new way of creating a vaccine and a brand new setting for creating a vaccine. So it’s a phase one trial, and phase one trials are really trails of brand new therapies. The goal of a phase one trial is not necessarily to see whether a new treatment can change survival in a large population, as these are very small trials typically. Rather, it’s more to test whether a new therapy is a safe treatment and if it’s a feasible treatment. Because this vaccine is a more involved vaccine—it’s a vaccine that’s given over many different visits over the course of six months—feasibility was a big concern.
How many times over six months?
MARRON: So the vaccine’s given 10 times. And each time you get a vaccine, it’s actually two days worth of visits. And so it’s a time-intensive commitment on our patients’ part.
Do you have any early data yet or anything that looks promising to you
MARRON: So there’s a few things that were promising. First of all, like I mentioned, there’s a few different endpoints. So safety is one of them. We obviously never want to give somebody—particularly somebody who may be cured of their cancer and we’re just worried about it coming back—a novel therapy that may give them really bad side effects. This vaccine was very well-tolerated other than some mild injection site reactions where we gave them the vaccine, but nothing like we’re seeing with COVID; I would say milder than most people even have a reaction to the flu vaccine. So it does seem safe. Additionally, it did seem feasible. There’s a lot of moving parts in this, as not only do we have to take their tumor and take their blood and do lots of in-depth genomic analysis of it, we then had to identify the optimal vaccine, and we actually had it synthesized in Germany and then sent over. And so there’s lots of moving parts, but we were able to create vaccines for all 15 patients that were enrolled in this trial. And while two patients were not able to receive the vaccine, we were able to give it to 13 patients, and nearly all of them received all the vaccines over the course of six months. So it did seem feasible. As far as efficacy, it’s tough to be 100 percent sure if something is effective or not when you’re looking at a small population. But one of the things that we have shown is that, in the first few patients that we’ve treated, we are actually able to track their vaccine responses in their blood. So we can actually look in their blood and see the expansion of the part of their immune system that’s recognizing their cancer the same way that we can do blood tests after getting the COVID vaccine and see development of antibodies and expansion of your T cells that recognize COVID. We’re able to show that against the components of the vaccine that we created for these patients. So we think that we’re successfully vaccinating these patients, and that’s really the goal, not only to hopefully eliminate micro metastatic disease—the microscopic bits of disease that are residing still in their body—but also if the cancer does come back, hopefully we can potentiate their response to further therapies, probably immunotherapies for most of these patients. We’re still in the process of analyzing all of the blood specimens from all of the patients. We have thousands of blood specimens from the patients over the course of over a year for each patient. And so there’s still a lot of work to be done in the laboratory. But our initial data does show that after getting all 10 vaccines patients can be very strongly immunized against their cancer.
What’s the benefit to having something like this available?
MARRON: Personalized cancer vaccines are obviously very attractive because we’re making an immunotherapy that’s targeted specifically for a patient. Cancer immunotherapy, as people know from all the advertisements on television, has really has revolutionized the way in which we’re treating cancer patients. The immunotherapies that we have that are FDA approved right now, that we use in patients with lung cancer, kidney cancer, bladder cancer, skin cancer, among others, these therapies are not personalized, and they don’t work for everyone. We think of these therapies as “taking the break off the immune system” but I think that one of the reasons they don’t work for many patients is that some patients don’t have a pre-existing immunity—so we are “taking the breaks off” an uneducated immune system. Now that we know this vaccine approach is safe and feasible, we’re now trying in a subsequent trial to combine the standard immune therapies that patients are receiving in the clinic for metastatic disease with these personalized vaccines, because we think that that combination probably is going to be the most effective approach.
Pave the way for, down the road, a vaccine for people who are high risk of cancer but have not developed cancer yet? What’s the potential for this information and for this research?
MARRON: So I think that’s an exciting idea. Obviously, preventative approaches are the most desirable approaches when it comes to cancer because, by the time that a patient has developed cancer, they have a significantly worse prognosis than if we’re doing things like an HPV vaccine, for instance, or identifying some sort of vaccine that we could give smokers that would decrease the likelihood of them developing cancer eventually. I think right now our focus is really on patients that do have cancer and identifying if it’s feasible, in a large-scale setting, to make personalized vaccines like this. Even if we are not able to make perfectly personalized vaccines, we can potentially use this pipeline that was developed by Dr. Bhardwaj and her colleagues in the OpenVax group to make a more off-the-shelf treatment that could be used in all patients. There’s certain mutations or changes in your DNA that are very common in lung cancer, in pancreatic cancer and in colon cancer, amongst others. If we could use this pipeline to develop a personalized vaccine that would target things like KRAS and P53, which are the genes that are commonly mutated in cancer patients, we would have a vaccine that could be administered across the globe regardless of ability to sequence tumors and do the in depth personalized analysis we do.
Are you able to speak to the patient’s case? Are you able to tell us a little bit about him, about his cancer, and about what he’s doing in the trial?
MARRON: He developed stage two lung cancer. And this is a cancer that normally we will remove from the body and then, afterwards or before, we will give chemotherapy as well. And so we give chemotherapy because we know that there’s a very high chance of this cancer coming back. Stage two cancer has already spread from where it started to the lymph nodes, and so we worry that tiny bits of it may have spread elsewhere in the body. And eventually six months down the line, one year down the line, the cancer may come back. So those patients typically, you know, before or after surgery, will get chemotherapy. But what people don’t realize is that chemotherapy, while effective, really only decreases the likelihood of it coming back by about five percent. So let’s say you have a 60 percent chance of it coming back, it really only brings that down to 55 percent. And so it’s still a very high chance of it coming back. And so I think that this population in particular is an ideal population to study these vaccines in because we want to bring that 55 percent significantly lower, ideally down to zero, so that we never see this cancer come back
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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