CAR-T Meeting 2026 | Affinity-matured CD72-targeting nanobody CAR T-cells in antigen-low B-cell malignancies

Disclosures

So when it comes to B-cell cancers, we know that CAR T-cells targeting CD19 have obviously been incredibly important for the field, and many patients have gone into long-term remission being cured by these CAR T-cells. But again, about half, depending on the indication, sometimes more than half, particularly B-cell lymphomas, patients are not cured by CD19 targeting CAR-T. So again, what we’re really focused on is how can we find alternate antigens for CAR-T targeting? And so for B-cell cancers, several years ago, we used our cell surface proteomics methodology, where again, we can basically analyze thousands of proteins on the surface of tumor cells. We identified this protein called CD72 that others hadn’t recognized before and we thought to be particularly promising for these refractory B-cell cancers. Because one thing we found, and we showed in the recent publication, is that some patients who are treated with CD19 CAR T-cells, when their tumors relapse, they no longer express CD19, so you can’t treat them with a CD19-targeted therapy. But those patients, they tend to still express high levels of CD72. And in particular for B-cell acute lymphoblastic leukemia, there aren’t really great options for a second-line antigen. Many groups have looked at a protein called CD22. But in general, the clinical results haven’t been super encouraging. Patients can get remissions, but they tend to be very short with CD22-targeted CAR-Ts. We think CD72 has many potential advantages over CD22. So that’s, we’re excited about CD72. 

In the recent paper, what we found was that in our preclinical work in the laboratory, when we treated mice with these CAR-T’s, when we did get relapses, sometimes we found they also would have lower levels of CD72 at the surface of their tumor cells. So what we tried to do recently was use protein engineering approaches where we could take our antibody fragment that recognizes CD72 that we put onto our CAR T-cell, and we could try to engineer that to make it what’s called higher affinity, so it binds more tightly. And the hypothesis was that we ended up showing is if we made this higher affinity antibody fragment, we could actually kill more of those tumors that had low density of CD72. So we’re excited about the potential of those to bring to the clinic. And this is something that we are trying to bring CD72 targeting CAR T-cells to clinical trials at my institution at University of California, San Francisco.

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