Periodic Reporting for period 4 - CHEMCHECK (CHECKPOINTS IN CHECK: Novel Chemical Toolbox for Local Cancer Immunotherapy)
Période du rapport: 2021-01-01 au 2021-12-31
Our isotype and species switched chimeric multimodal fluorescent and SPECT immunoimaging Fab and mAb constructs targeting mPD-L1 will enable us to monitor the immunomodulatory changes in the tumor microenvironment in response to our interventions in longitudinal studies. An evolved opportunity is the translation of these multimodal imaging tools towards photodynamic theranostic tools enabling image guided photoimmunotherapy. Proof of concept for this approach was achieved with anti-mCTLA-4 antibody fragments. We will continue our efforts to synthesize multimodal conjugates for local and conditional activation of checkpoint inhibition, as well as the ‘second generation’ cysteine cathepsin targeted photodynamic activity-based probes. All these tools will be evaluated in our 3D cancer immune cell co-culture system. We will further unravel the proteolytic changes during tumor-associated macrophage re-polarization in our 3D co-culture system and the significance thereof to the anti-tumor mechanism of this strategy. Ultimately, we will combine these strategies in the optimized preclinical models for in depth immunological characterization. We expect to identify multiple novel molecular immunomodulators, which together will form a highly dedicated symbiotic immunotherapeutic regime.