EHA 2019 | Targeting FLT3 in AML

We are interested in T-cell recruiting antibody constructs for treatment in AML, and we are currently recruiting patients into CD-33 T-cell recruiting antibody constructs for relapse refractory AML, but clearly, CD-33 is a difficult target antigen because it’s ubiquitously expressed also within the healthy hematopoietic system. So FLT-3 might be a more promising and more restricted target antigen. And in the work we presented here at EHA, we looked at the FLT-3 specific, bio-specific T-cell recruiting antibody construct in our pre-clinical setting. And we could show that it very efficiently kills autologous AML cells, but we’ve also been interested if we can augment a FLT-3 bite by combining these with tyrosine kinase inhibitors, which as you know, have already been approved for primary therapy in combination with chemotherapy.

So what we could show in our work is that the addition of tyrosine kinase inhibitors, and we tested several ones, can have an additive effect when we are utilizing FLT-3 bites. We were worried that these TKIs can also compromise T-cell function, and we could identify a therapeutic window where we can enhance efficacy and cytotoxicity of primary AML cells with a certain dose of the TKI, which then enhances the FLT-3 bite mediated cytotoxicity. And in previous work, we could show that one of these mechanisms is due to the fact that FLT-3 has an increased expression on the surface. So one mechanism at least in the increased expression of FLT-3 on the surface, and there might be other beneficial effects by modulating the T-cell compartment. So we think this is a strategy that should be translated into a phase I trial.