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This combination therapy regimen, evaluated in the ELI trial (NCT05248230), is a multi-modal approach for treating proficient mismatch repair (pMMR) metastatic colorectal cancer. It combines the PD-1 checkpoint inhibitor pembrolizumab with two physical ablation techniques: calcium electroporation (CaEP) and irreversible electroporation (IRE). CaEP involves the intratumoral injection of calcium chloride followed by reversible electroporation, which facilitates massive calcium influx into cancer cells, leading to ATP depletion and immunogenic cell death. IRE uses high-voltage electrical pulses to induce permanent nanopores in the cell membrane, causing apoptotic cell death while sparing the extracellular matrix. The primary goal of combining these ablative techniques with pembrolizumab is to stimulate a local and systemic immune response (abscopal effect), potentially converting "cold" pMMR tumors into "hot" tumors that are susceptible to immunotherapy.
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