What are CAR T cells and how are they made? CAR T cells are gene modified T cells. The acronym CAR stands for chimeric antigen receptor. So these are basically cells that on the outside have an antibody. And normally antibodies are not found on T cells. They're only found on B cells. So you take this antibody and it's been genetically engineered to be attached to a component on the inside of the cell that has the signaling mechanisms, the components that actually allow the T cell to become activated and to do what it needs to do. So it's chimeric because it's got a B cell component on the outside and a T cell component on the inside. Because it has this antibody on the outside, it can target a protein. The benefit of a CAR T cell is that you can make one CAR and potentially put it into everybody's T cells and that same one CAR can work in every single patient. Now what CAR T cells are not, however, is universal. In other words, the same construct can work for me and you and everybody else, but it has to be with my cells for me and your cells for you. So that's a limitation of CAR T cells is that it's put into T cells and so it amplifies T cell responses. It's done in a patient specific manner and the results thus far have shown that it is very effective in eradicating tumor quickly. I think the problem in myeloma is that we're not seeing the cure rates with CAR T cells in the data at least that's been presented thus far compared to acute leukemia in children and lymphoma in adults. What is the chimeric antigen receptor? The way that the CARs are constructed, there's a part of this chimeric antigen that is on the surface of the T cell and another part that's kind of embedded on the inner side of the cell membrane. And both of those parts can be modified to become more specific and active against the target cells. So that's where the field has gone from first, second and third generation and it's really the second and third generation CAR data that we have in the public domain for lymphoma and myeloma. Are all CAR T cells the same? All CAR T cells are definitely not the same. I think we're in some ways in our infancy or at least in our early childhood with respect to understanding how we can use this therapy and use CAR T cells to get after the cancer and lots of different centers have different approaches, different targets that they might go after as well as differences in how the CAR T cell is generated or designed. It might bind different parts of BCMA. It might bind something other than BCMA. Beyond that, there are features that allow us to have the CAR T cell get either closer or further away from the target cell and it turns out that makes a difference, proximity to the target cell. Those might be differences. There are a number of differences too in how they get activated or turned on to engage in their attack and that might have significant implications with respect to two things. One, how many of those cells are generated after the T cells encounter the tumor cell, how fast they proliferate, how high a level they get to basically, the numbers of them, but then also maybe how long they persist and stick around for. So the features that we put into the design of the CAR T cells is very important and differs from center to center. The other thing that is different is how you actually generate those cells in the laboratory. Here at the Fred Hutch, we take a very specific approach where we try and divide the cells, separate them into CD4 and CD8 cells and then put them back together and re-infuse them into the patient. We believe that it's better to give it what we call a defined composition product to patients. We know the fraction of CD4 and CD8 cells and then we can follow them later on to see what they're doing. We also just think that that combination together, that they help each other work more effectively and efficiently and that's what we're doing on our trials.