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Aliya®Pulsed Electric Field (PEF) technology is an emerging strategy in the field of cancer treatment, offering a novel approach to ablation therapy that does not rely on thermal mechanisms. By employing a multi-stage experimental setup, including potato tuber, porcine liver, and murine breast cancer models, we explored the dose-response relationship on ablation and immune modulation by varying the pulse packets delivered from 20 to 100. The biologic response observed with 60 packets represented a minimum effective dose yielding reproducible ablation parameters, immune response, and efficacy which could be augmented with immune checkpoint blockade. This pre-clinical analysis provides a first step toward understanding the therapeutic index for PEF technology beyond ablation, a consideration that will require robust clinical validation in well-designed prospective studies.