Targeted treatment of AML using T cell recruiting antibody constructs

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Published: 19 Jun 2019
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Prof Marion Subklewe - LMU Hospital Munich, Munich, Germany

Prof Marion Subklewe speaks to ecancer at the 2019 European Hematology Association (EHA) Annual Meeting about using T cell recruiting antibody constructs for the treatment of AML.

She explains that so far T cell recruiting antibodies have been used to target surface antigens, but these have the limitation of not having a restricted expression profile.

To solve this problem, Prof Subklewe explains that they have been doing preclinical work with a novel T cell recruiting antibody construct which recognises an infracellular target antigen - WT1 - and so has a much more specific and restricted target antigen.

Prof Subklewe concludes by saying that she hopes this promising new information leads to a phase I trial.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

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.