The IL-12-encoding DNA plasmid tavokinogene telseplasmid resulted in robust tumor response (ORR: 36%, CRR: 18%) when electroporated into melanoma lesions in a phase II trial,549 and the efficacy was further augmented (ORR: 41%, CRR: 36%) by combining it with pembrolizumab.550 Intra-tumoral administration of saline-formulated551 or oncolytic nanoparticle-coated552 mRNAs encoding different anti-tumoral cytokines including IL-12 induced effective anti-tumor activity and potentiated the effects of ICIs in anti-PD-1-resistant tumors. The gene discussed is PDCD1; the disease is neoplasm.