Benefits of Alternative ADC Mechanisms Beyond Cytotoxicity: Rationale for RNA Splicing Payloads That Induce Cell Death & Activate Anti-Tumor Immunity
- The Hypothesis: Examine the scientific rationale for leveraging RNA splicing modulation as a novel ADC payload mechanism that delivers a dual anti-tumor effect through direct cytotoxicity and immune system activation, offering differentiation beyond traditional microtubule inhibitors and DNA-damaging payloads
- The Journey: Engineering desired features such as MDR resistance and development of payload-specific conjugation strategies. Why cleavable vs non-cleavable strategies need to be revisited for each novel payload.
- The Pay-off: Early translational and preclinical data supporting anti-tumor cytotoxic activity, including evidence of immune activation and activity across oncogenic driver-driven cancer models
- Future Directions: How next-generation RNA splicing modulator payloads could expand the ADC therapeutic landscape through differentiated mechanisms of cell death, potential combination synergy with immunotherapies, and opportunities for broader antigen targeting strategies