Sialic acid receptors Siglec-7 and -9 as targets for immunotherapy
The research team studying Siglec – Sialic acid axis as novel immune checkpoints in cancer led by Prof. Gosse Adema teamed-up with Aduro Biotech Europe, a biotech company continuously evaluating novel immunotherapy targets to add to their research pipeline. As part of this partnership, this project was established to generate and analyse the potential of dual blocking antibodies simultaneously neutralising Siglec-7 and -9 for immunotherapy of cancer.
Despite all the advancements in the field of cancer immunotherapy, still the majority of cancer patients does not respond to immunotherapy. This leaves open a tremendous societal and economic potential for new kinds of cancer immunotherapies. Thus calling for novel approaches that either potentiate the efficacy of existing immune checkpoint inhibitors or to new biologicals modulating novel classes of immune checkpoint regulators.
This project aims to develop dual-specificity mAbs that have the potential to target two novel immune-inhibitory receptors Siglec-7 & -9 at the same time. Therefore, as a proof of concept for this strategy, antibodies were selected with the capacity to simultaneously neutralise Siglec-7 and -9. Further, antibodies were functionally characterised and receptor and ligand expression of Siglec-7 and -9 was analysed in the tumor microenvironment in human cancer.
Generation of antibodies using Aduro’s antibody development platform yielded a set of Siglec-7/9 dual targeting antibodies (Deliverable 1). To further study the functional impact of these mAbs in a cellular context (Deliverable 2), tumor cell/immune cell co-culture assays have been developed and the dual-specific mAbs lacking the Fc-part have been generated. Experiments to provide insight in the functional impact of co-blocking Siglec-7/9 using these dual-targeting mAbs are currently ongoing. Finally, the data sets of the RadboudUMC confirm the expression of both Siglec 7 and 9 and their Sialic Acid ligands in the tumor microenvironment (Deliverable 3), pointing out the potential for the use of Siglec-7/9 blocking antibodies for cancer immunotherapy in the future.