What are cancer vaccines and how do they work? What side effects are being seen with myeloma vaccines? Have any cancer vaccines been FDA approved?

What is a vaccine? So I think people are familiar with the notion of a vaccine to protect against infection. We get those as kids to protect against things like measles or mumps and now there's been of course an experience with the COVID pandemic and how what a critical place vaccines have played in that. And the notion there is that you're trying to train the immune system to see an infection as something that is foreign and something you need to be protected against. And so we essentially educate the immune system to be prepared that if that pathogen, if that infection arises, we have cells that are there for the ready to protect and get rid of that infection and also to provide memory so that if that infection is re-experienced, you're ready for it. We're essentially trying to do the same thing in cancer, which is to essentially train the immune system to see cancer cells as foreign, to raise a population of immune cells, often known as T cells, to be having already been prepared to see that particular feature of a cancer as something to go after or something foreign and then to attack it and also protect against its re-emergence. Are vaccines a type of immunotherapy? It's a type of immunotherapy, exactly. How do cancer vaccines work? So I think people have become more and more familiar with how the immune system can attack cancer. So for instance, things like CAR T cells or T cell engagers, we call bytes, are about raising a population of immune cells that you directly infuse into the patient. In a vaccine, what we're trying to do is educate the immune system inside the patient by introducing parts of the tumor, for instance, an antigen or a protein that's on that tumor, or taking the whole tumor cell itself and introducing it to the immune system in the patient in a way that the patient can now see it. Cancer cells are often present in a way that's very difficult for the immune system to see. They essentially hide and they create a bubble around themselves that make them very difficult to detect. What a vaccine is trying to do is take pieces of the tumor or the whole tumor itself, reintroduce it to the immune system, often with things that will stimulate the immune system, stimulate teachers of the immune system known as dendritic cells, and to drive an immune response inside the patient's own body. And that those T cells that are then stimulated can fight against the malignancy, but also then be an army that's there at the ready at time of potential relapse. So vaccines in general are a means of eliciting an immune response. The way that you do that, whether it's for tetanus or measles or for cancer, is to take some bits and pieces of whatever it is that you're trying to kill or trying to get control of. And that can be the whole cell that's inactivated. As we know now with COVID, that can be what they call mRNA. And the mRNA then in the vaccine gets inside different immune cells and has those cells produce the abnormal proteins that are part of COVID. And that allows the immune system to recognize these proteins and say, okay, I'm going to bond an immune response to this. With the myeloma vaccine, which I'm involved with, some years ago, Ivan Burello and colleagues took bits and pieces of myeloma cell lines. So these were bits and pieces of myeloma cell lines that had been taken from patients who had aggressive myelomas from many years ago. And these were studied in different settings. What they did was when they took these cell lines, they mixed them with another cell that produces a substance called GMCSF. And now what all these things mean is that you take bits and pieces of myeloma and another cell, you mix them all together, and this other cell makes this GMCSF. And GMCSF is kind of like a Kickstarter. It's what we call an immune adjuvant. When you put all this stuff together, put it in a shot and give it to a patient, then the GMCSF, which is being produced by this cell, along with bits and pieces of myeloma tells immune cells in the vicinity, hey, come over here. This is myeloma. It's right here. You've just been injected with dead myeloma cells. And the immune system, under the influence of GMCSF and in its environment where it finds dead myeloma cells, looks at these and goes, you know what? This looks bad to me. This is something that we need to learn how to fight. So these are antigens. And the immune system is exposed to them. And the immune system says, hey, look, let me mount an immune response. Let me mount, develop, train T cells, which we have all heard of. They help us fight infections and cancers to develop a response to these antigens or make other cells, which might make antibodies to these antigens. So all of this immune response then slowly begins to develop. And just like you may see with whether it's measles vaccines or hepatitis vaccines, there is more than one shot. So the initial shot exposes the immune system to these antigens and the immune system says, aha, I know what I'm supposed to do. And subsequent shots are booster shots that train the immune system even better to mount a long term immune response. And that is the goal of vaccines in general, cancer vaccines as well, and very specifically this anti-myeloma vaccine, GVACS. The G in the GVACS comes from the GMCSF, which is part of the vaccine construct. Do vaccines reduce tumor burden? Vaccines work by stimulating the immune response to better recognize and kill the myeloma cell itself. I think if you think about how vaccines work in the prophylactic setting, what it does is that it trains our body to either generate antibodies or to generate T cell responses so that when our bodies ultimately see that thing that we've been vaccinated against, or influenza, that we can much more quickly mount an immune response and effectively kill that virus or bacteria or whatever it is that we're trying to kill. In terms of tumor vaccines, the concept is a very different one. We are trying to augment the ability to eradicate the disease. And the way it's being done is by training the immune system to more effectively recognize the tumor and kill it. And so it does work through killing the tumor cells. It probably works through killing tumors that are present at a relatively low disease burden. What side effects are being seen with myeloma vaccines? So I think in contrast to CAR T cells, which as I mentioned to you, can have patients hospitalized in the ICU, and some of the problems that we've seen with the checkpoint inhibitors or the PD-1 where, as I mentioned earlier, the FDA closed the trials down because of increased mortality. What we're seeing with vaccines is a very, very tolerable side effect profile. Virtually the side effects are limited to some local injection side reactions, redness, itching, and that's pretty much it. So in this spectrum of things, they are probably the safest therapies that we currently have available in the realm of immunotherapy to treat patients with multiple myeloma. Have vaccines been used in treating myeloma? There were two examples of a vaccine. One in prostate cancer and one in melanoma that did receive approval. These I think are clearly works in progress. In other words, they showed some effect. But what the whole field is really sort of experiencing now is that there's been a fundamental change in our understanding of the biology of how the immune system works in cancer. And so even things like checkpoint inhibitors, which became a huge way we treat certain solid tumors, didn't exist 10 years ago because we didn't understand that that was an important way that the immune system was educated. These in some ways are much older and there's a long history of people trying to apply them and not working very well because they didn't understand some of these other principles. Things that stimulate the immune system or things that are part of the cancer environment that prevent the immune system from working well were not part of those original vaccines. And so what we're hoping is that this newer generation will take those pieces, maybe integrate with some of the other therapies and be successful.