We are very interested in utilising T-cell recruiting antibody constructs for the treatment of AML. So far what’s around in clinics are T-cell recruiting antibody constructs targeting surface antigens, so mostly it’s CD33 and it is also CD123. But they have the limitation that they don’t have a restricted expression profile so it’s also expressed on a lot of healthy… haematopoietic system is expressed in the spleen is expressed in the liver. So this is a challenge in targeting AML.
We have now done preclinical work with a novel T-cell recruiting antibody construct that is actually recognising an intracellular target antigen, WT1, which is processed and presented in the context of HLA-A2 on the surface of AML cells, thereby having a much more specific and much more restricted target antigen. In previous work it has already been shown and addressed targeting WT1 in the context of HLA-A2 in AML but with limited efficacy. So the nice thing about this novel antibody construct, which was developed by Roche and we did the preclinical testing, is that it’s targeting the antigen bivalently, thereby increasing the avidity to the target antigen enormously. So we’ve compared WT1 specific T-cell clones to these antibody constructs which are recognising, as I said, bivalently this target antigen and could show that we have a very high cytotoxicity of primary AML cells, proving that this target antigen is actually expressed on primary AML cells with a sufficient amount to at least be recognised by our bispecific antibody construct in mediating high cytotoxicity.
So we think this is a very interesting novel approach for treatment of AML and we are hopefully going to initiate a phase I trial.