Potent anti-cancer therapy created using 'click chemistry' uclnews NatureChemistry
In the field of T cell redirection it has been shown that blockade of the PD-1/PD-L1 immune checkpoint is synergistic with BiTE treatment. Target cells not constitutively expressing PD-1 can upregulate this immunosuppressive protein following the addition of BiTEs. Based on these observations, the generation of fusion proteins with an anti-CD33 BiTE core combined with a PD-L1-blocking antibody fragment were generated.
However, these three-protein conjugate platforms do not incorporate an Fc fragment or similar half-life-extending functionality, and might require other approaches to improve pharmacokinetics. Many parameters have to also be considered for their construction , such that the addition of small molecules to either modulate function, provide theranostic capabilities or just as tools to allow for monitoring of the biodistribution of these species could prove beneficial.
. Additionally, few CiTEs have been described in the literature and there are thus many combinations of checkpoint inhibitor and BiTE that are yet to be explored. Among these is the checkpoint inhibitory enzymeThus, we set out to develop a chemical method for the attachment of an additional protein to a BiTE core . The method developed allowed for the introduction of small-molecule functionality to these three-protein constructs .
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