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COMy 2025 | Unique features of the D-domain BCMA-directed CAR-T construct anito-cel
Binod Dhakal, MD, Medical College of Wisconsin, Milwaukee, WI, outlines the unique features of the D-domain BCMA-directed CAR T-cell construct anitocabtagene autoleucel (anito-cel) that make it an attractive candidate for the treatment of multiple myeloma (MM). These include its small size, stability, high transduction efficiency, and high surface expression. This interview took place at the 11th World Congress on Controversies in Multiple Myeloma (COMy) congress in Paris, France.
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Transcript
So D-domain stands for de novo derived synthetic domain. So this is a little bit different than the traditional single cell variable fragment or SCFV domain because it’s synthetic compared to the SCFV which is mainly derived from the humanized or the mouse or even the human. So that is the unique part. The other part about it is there are a few attributes that make it unique...
So D-domain stands for de novo derived synthetic domain. So this is a little bit different than the traditional single cell variable fragment or SCFV domain because it’s synthetic compared to the SCFV which is mainly derived from the humanized or the mouse or even the human. So that is the unique part. The other part about it is there are a few attributes that make it unique. Number one is it’s very small in size and it is stable. It is very stably expressed, even under both physiologic and extraphysiologic conditions. And because of that, and because of the protein structure, the CAR is expressed, you know, the transduction efficiency is very high. And the amount of surface density of the CAR in the cell is quite big, so quite high expression of the CAR in the cell. So that means you have a CAR with a high transduction efficiency, high surface expression. In addition, in the preclinical models, we also found that this domain with the BCMA, the ddBCMA CAR, has a low risk of tonic signaling and that’s why a low risk of exhaustion. So that means you can achieve many contact points and kill a lot of cells very effectively with a low risk of exhaustion over repeated killing. So these are some of the attributes of this D-domain binding and hence the D-domain BCMA CAR.
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