What are antigens and neoantigens?

What are antigens and neoantigens? In cancers in general, what we've come to understand is there are two types of proteins that can be recognized by the immune system. These proteins that can be recognized by the immune cells are called antigens. And there are common antigens and then there are patient-specific antigens. So the common antigens would be that if we take all myeloma patients, roughly 60-70% of them have things that are uncommon. That would be like saying if we take a population of individuals, we could all say that they have a head and two arms and two legs and two ears. But then what we have to ask ourselves is are those heads and arms and eyes and ears all the same? And that's where you get these differences. These differences are known as neoantigens. Basically what's happening is that our body, as it's going from a normal cell to a cancer cell, has some dysregulation of the way these proteins are being made to the point that some of these are unique. And they can be unique in terms of signaling to the cancer cell, to the myeloma cell itself, to the polyphery board. And they can also be unique in the sense that they can generate a new immune response that can be seen by the T cells themselves. Antigens are very interesting and have actually developed a lot of interest even scientifically. And the reason for that is because they're unique. So each one of us with our cancer has a specific set of antigens that only we have. And so those neoantigens are antigens that are probably much more likely to generate an immune response if we can actually identify them and vaccinate them. And so there have been examples in melanoma as well as glioblastoma, the brain tumors, where studies have been done identifying, synthesizing, and then vaccinating against these neoantigens. And it's been shown that as we generate these responses, we can get much more potent antitumor immunity. Now, the problem is that doing this is very labor intensive. And obviously, every individual has a different neoantigen. So you can't just make a pool of these things and use them as a vaccination. An antigen is a specific protein on the outside of a cell that is bound up by an antibody. So antigens and antibodies bind each other much like a lock and a key. Any antibody has to have a specific antigen for which it will bind. So when cells express antigens, then our body, if they have an antibody to it, will have a specific response to that cell and no other cell because only a certain cell would have that antigen. Do all types of cells express the same antigens? There are millions upon millions of antigens. And theoretically, we have antibodies to all of these. They're all specific, though. So every cell will have a specific type of antigen, multiple types of antigens, but they're not all the same. And they all should be very specific for that specific cell type. BCMA is an antigen that's present on plasma cells, both normal plasma cells as well as multiple myeloma cells. It's hardly expressed anywhere else. It's predominantly only in the plasma cells and myeloma cells. So that makes it an excellent target to use because you want targets that are only present on the myeloma cells and not anywhere else because then if we have an antibody that we develop to that antigen, it's going to be very specific to the myeloma cells. What is a neoantigen? A neoantigen is an antigen that's produced when there's a mutation. Antigens are proteins. And these proteins get produced when you have translation of mRNA. And then some of these proteins will go to the cell surface. And if they go to the cell surface, then they're an extracellular antigen. You can have intracellular antigens as well. But when you have mutations, you can form what's called neoantigens, which are sort of mutated versions of normal antigens. That can be good or bad because a neoantigen may not, unfortunately, be recognized by a classical antibody, but it also may be different enough where it can be targetable. Is BCMA the only antigen on myeloma cells? So myeloma cells express lots of antigens. And we're trying to find ones that are specific to myeloma cells because, again, any antigen that's present on normal cells will potentially cause damage if we target that because those normal cells will also be affected. So some of the other antigens that we're looking at, CD38, is an antigen that's present predominantly on myeloma cells. That's the target of some of the antibodies that we use for treatment. There's some other ones that we're currently investigating that are really exciting. BCMA, obviously, is the most novel, newest one that has some recently approved agents that target it as well.