In order to achieve enhanced antitumor effects, administration of high doses of IL-2 is imperative, leading to elevated concentrations of IL-2 in the bloodstream and subsequent manifestation of adverse reactions in patients, including asthenia, pyrexia, and potentially life-threatening toxicity such as capillary leak syndrome.248 To mitigate the systemic toxicity associated with IL-2 protein delivery, Shin et al.249 proposed a novel approach involving intratumoral administration of IL-2 mRNA NPs. This evidence concerns the gene IL2 and Fever.