How are vaccines made? What are vaccine adjuvants (immune stimulators)?

How are vaccines made? So there are different ways that it can be made. One really basic part is you have to isolate either a part of the whole tumor and then reintroduce it to the patient with some kind of immune stimulant. So in the example of what we've been working on, just as an example, what we do is we take tumor cells from a patient and we mix them or fuse them together with powerful teachers of the immune system called dendritic cells. And those dendritic cells, which normally live inside of us, can also be grown outside the body. And so we take the patient's tumor, we take their dendritic cells, we incubate them together with a special molecule that dissolves their membranes and then allows them to reform. So now we have a cell that's half cancer and half immune stimulant. And those cells can be injected in the body and will stimulate or drive T cell responses. So that's an example of a vaccine. Another example, which has been an area that people are very interested in, is finding mutations in a cancer and showing that those mutations make proteins that are completely new for the body and using those proteins as a driver of an immune response, what we call neoantigens. Those neoantigens, again, can be introduced with ways that stimulate the immune system. And so you're taking things that are unique to the tumor and then stimulating the immune system around them so the patient will make an immune response. As an example, when we do our, what we call, fusion vaccine, we take a patient-derived myeloma cell and we mix it and fuse it together with the patient's own dendritic cell. There are other examples of myeloma vaccines where pieces of the myeloma, certain proteins, for instance, there's a protein called MAGE A3 that's been used to make vaccines. One of the, I would say, challenges is that when you're stimulating the patient's own immune system, one of the hurdles you have to get over is how well does their immune system work? Will it respond to a vaccine? This was an important issue, for instance, with COVID, where people said, well, would a myeloma patient respond to the COVID vaccine or do their T cells not work as well? And is that part of the reason why they have myeloma to begin with? So if you're using a vaccine, you have to be mindful of that. And a lot of the strategies now have been to take a vaccine and maybe mix it together with strategies to help the immune system function better. What are vaccine adjuvants or immune stimulators? We use the word adjuvant. What it means is that you're trying to do something that will stir up the immune system. We know the tumor is present inside the body and it has its antigens on it, but somehow it's not causing a response. Otherwise, you'd make a response. Interestingly, we know that some myeloma does actually induce a response. And we think that one of the things that causes myeloma to grow more aggressively is when that response starts to disappear. So when we look at the stages of myeloma development, often early on, there is an immune response that's keeping it in check. And later on, that immune response is lost. So the vaccine is trying to restart that immune response. So you need something beyond just the protein or the adjuvant to stir up the immune system. The adjuvant, I should say, is a way that is something that stimulates inflammation and will drive that response. The dendritic cell is almost another form of an adjuvant, a living adjuvant, that basically takes up that antigen and presents it to the immune system in a way that tends to be more effective. What are dendritic cells? So dendritic cells are teachers of the immune system. The way the immune system works is that when a T cell meets a potential target, it looks for danger signals. And if it doesn't see those danger signals, it thinks what it's meeting is friendly and it leaves it alone. In fact, that's how when we have T cells that meet, for instance, our own skin or other tissues, they know to not get activated, to not kill. So what a dendritic cell does is it's a teacher for the T cells of what to leave alone or what to go after. It often is loaded with those stimulatory signals that tell a T cell, when you see this protein, when you see this antigen, get excited, go after it. If you see this one, don't get excited. So it's a very important tool if you're trying to re-educate the immune system to see tumor cells as foreign or their antigens as foreign, dendritic cells can be very powerful teachers. They are blood cells. They migrate throughout the body. They often live initially at sites where disease comes in, for instance, like the respiratory epithelium or the skin. And then when they meet their antigen, they travel to lymph nodes where they then meet T cells and stimulate them.