One remarkable example of such project deliverables is an immune-cell targeting agonistic antibody campaign. The mode of action of agonistic antibodies is often described to be restricted in hitting epitopes of the natural ligand, to include internalization of the antibody, and to require amplification of the agonistic activity by accessory Fc-receptor interactions. Strikingly, in the set of the resulting top-ranking humanized, functional, agonistic antibodies, we observed a huge diversity with regard to the antibody internalization profile and competition with the natural ligand. Most importantly, some antibodies confer unrivaled, strong agonistic activity on primary immune cells, even when they carry Fc-modifications which do not allow accessory Fc-receptor mediated amplification.

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