Fig. 3: ADC directed trimodal chemo-radio-immunotherapy.

Trimodal chemo-radio-immunotherapy treatment package consisting of systemically delivered radiosensitizing ADCs given together with conformal radiotherapy followed by immunotherapy. ADCs combined with radiotherapy produce receptor restricted radiosensitized immunogenic cell death depicted at the cellular level (top). After initial receptor mediated ADC internalization, linker cleavage releases free drug that can diffuse into surrounding tumor cells producing bystander cytotoxicity and radiosensitization in a receptor-independent manner. ADC drug payload radiosensitized tumor kill stimulates tumor immune infiltration and in concert with immune checkpoint inhibitors improves tumor control in a receptor-independent manner. Translation potential of ADC directed trimodal precision chemo-radio-immunotherapy with current clinically approved ADCs (bottom).