CAR-T Meeting 2026 | Searching for the optimal CAR-T target in multiple myeloma: promising antigens being uncovered

So in general, we know for multiple myeloma, especially here, we’re here at the European CAR-T Congress, and so when it comes to CAR-T cells, BCMA is the king, right? But the issue is we know that most patients are not going to have a long-term remission after BCMA-targeted CAR-T. So the big question that we need to address for patients is what’s the best alternate target if BCMA CAR-T has come and gone? And so that’s the thing that we focus on very heavily in my lab. And we know that there are promising targets that are out there already, such as GPRC5D being most advanced. Another exciting one that I like a lot is called FCRH5. But we have therapies directed against those, not CAR-T cells that are approved yet clinically, but they’re going to come soon. But the question is, we still don’t know if they’re the optimal second-line antigens. And when we say antigen, I’m talking about a protein on the surface of myeloma plasma cells that we’re able to target with a CAR-T. So BCMA is one such protein, GPRC5D, FCRH5. 

So what we’ve done in my lab, we use a technology called cell surface proteomics. And basically what this means is we can take an instrument that historically has been used for analytical chemistry, but now we can apply it to cancer biology. And we can identify thousands of these antigens or proteins on the surface of myeloma tumor cells, and then use computational methods to try to decipher which ones could be promising alternate targets for multiple myeloma, maybe that other people haven’t found before. And so what I’m going to talk about here at the meeting is we’ve identified one target called CCR10 that no one else had previously identified as being promising in multiple myeloma. We found not only does it look to be a very promising target in multiple myeloma, but we can use AI-based approaches to actually design CAR T-cells against CCR10 that we couldn’t have done otherwise, and so we think it’s very exciting. 

There’s another target that we’ve published on just this past year called CD70 that also came out of our surface proteomics screens. We took advantage of data from the Multiple Myeloma Research Foundation COMPASS study to specifically find that CD70 looks most attractive for patients who not only have relapsed on BCMA-targeted CAR-T, but have some of the high-risk genotypes, so basically changes in the DNA of their tumor that drive relapse. Those patients tend to express higher levels of CD70 on their tumor, which means that using a CD70-targeting CAR-T is more likely to be effective for them. 

And then finally, the last thing I’ll talk about is one question right now that we have when it comes to target finding is can we go beyond even just what we call the expression level, basically how much of that antigen or protein is there at the surface, but trying to uniquely think about features or shapes of those proteins that may be only on myeloma plasma cells, even if that protein itself is on normal cells that you don’t want to target them because you’re going to get bad side effects. But what if there’s unique features of the proteins on myeloma plasma cells? So we’re developing new technologies in our laboratory that let us identify different three-dimensional shapes of those proteins on the surface of plasma cells that we can develop next-generation technologies against. So I’ll talk about a specific shape of this protein called CD48 that we believe we discovered and we’re trying to target. So that’s really what I’m going to talk about for targeting in myeloma.

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