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EHA 2019 | AML: Targeting Wilms’ tumor 1 with WT1-TCB

Marion Subklewe, MD, Ludwig Maximilian University Hospital Munich, Munich, Germany, discusses her work investigating targeting Wilms’ tumor 1 (WT1) with a T-cell bispecific antibody (WT1-TCB): ex vivo and in vivo potency by bivalent recognition of peptide-MHC complexes from an intracellular tumor antigen at the 24th Congress of the European Hematology Association (EHA) 2019, held in Amsterdam, Netherlands.

Transcript (edited for clarity)

So the problem in utilizing T-cell recruiting antibody construct in the setting of AML is the identification of a suitable target antigen.

So we have done preclinical work, utilizing a novel T-cell recruiting antibody construct that is actually targeting an intracellular antigen. So this is WT1, which is presented in the context of HLA-A2 on the surface of AML cells...

So the problem in utilizing T-cell recruiting antibody construct in the setting of AML is the identification of a suitable target antigen.

So we have done preclinical work, utilizing a novel T-cell recruiting antibody construct that is actually targeting an intracellular antigen. So this is WT1, which is presented in the context of HLA-A2 on the surface of AML cells.

So what this is, antibody constructs which has been developed by Russia where we did a preclinical assessment of this construct, we have a bivalent binding antibody construct that is mimicking the TCR and is recognizing MHC peptide complexes on the AML cells.

And this is previously already defined WT1 derived peptide that is presented in HLA-A2 positive patients which are about 50% of the AML patients.

And we could show, utilizing this antibody construct, that it is highly effective in recognizing and mediating cytotoxicity against primary AML cells. And interestingly, as TCR transgenic T-cells have been around and have already been applied in phase one trials for treatment of AML.

We could show that in comparison to a TCR specific T-cell clone, these antibody constructs have a higher avidity to the AML cells and are thereby more sufficient in mediating cytotoxicity in AML.

So we think that these antibody constructs are highly interesting because they open up an entire bag of possible target antigens which are derived from intracellular proteins and thereby might be more specific than the surface target antigens which we are currently addressing with T-cell recruiting antibody construct and by using this bispecific T-cell recruiting antibody construct we achieve a higher avidity even to antigens that have a low expression level on the AML cells.

So we are very excited about our preclinical data and hopefully we’ll initiate a phase one trial at the end of next year.

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