Briukhovetska, D. et al. Interleukins in cancer: from biology to therapy. Nat. Rev. Cancer 21, 481–499 (2021).
Oft, M. Immune regulation and cytotoxic T cell activation of IL-10 agonists—preclinical and clinical experience. Semin. Immunol. 44, 101325 (2019).
Oft, M. IL-10: master switch from tumor-promoting inflammation to antitumor immunity. Cancer Immunol. Res. 2, 194–199 (2014).
Autio, K. & Oft, M. Pegylated interleukin-10: clinical development of an immunoregulatory cytokine for use in cancer therapeutics. Curr. Oncol. Rep. 21, 19 (2019).
Naing, A. et al. Safety, antitumor activity, and immune activation of pegylated recombinant human interleukin-10 (AM0010) in patients with advanced solid tumors. J. Clin. Oncol. 34, 3562–3569 (2016).
Naing, A. et al. Pegilodecakin combined with pembrolizumab or nivolumab for patients with advanced solid tumours (IVY): a multicentre, multicohort, open-label, phase 1b trial. Lancet Oncol. 20, 1544–1555 (2019).
Naing, A. et al. PEGylated IL-10 (pegilodecakin) induces systemic immune activation, CD8+ T cell invigoration and polyclonal T cell expansion in cancer patients. Cancer Cell 34, 775–791.e773 (2018).
Fujii, S., Shimizu, K., Shimizu, T. & Lotze, M. T. Interleukin-10 promotes the maintenance of antitumor CD8+ T-cell effector function in situ. Blood 98, 2143–2151 (2001).
Berman, R. M. et al. Systemic administration of cellular IL-10 induces an effective, specific, and long-lived immune response against established tumors in mice. J. Immunol. 157, 231–238 (1996).
Emmerich, J. et al. IL-10 directly activates and expands tumor-resident CD8+ T cells without de novo infiltration from secondary lymphoid organs. Cancer Res. 72, 3570–3581 (2012).
Qiao, J. et al. Targeting tumors with IL-10 prevents dendritic cell-mediated CD8+ T cell apoptosis. Cancer Cell 35, 901–915.e904 (2019).
Guo, Y. et al. Metabolic reprogramming of terminally exhausted CD8+ T cells by IL-10 enhances anti-tumor immunity. Nat. Immunol. 22, 746–756 (2021).
Zhao, Y. et al. IL-10-expressing CAR T cells resist dysfunction and mediate durable clearance of solid tumors and metastases. Nat. Biotechnol. 42, 1693–1704 (2024).
Gorby, C. et al. Engineered IL-10 variants elicit potent immunomodulatory effects at low ligand doses. Sci. Signal. 13, eabc0653 (2020).
Spigel, D. et al. Randomized phase 2 studies of checkpoint inhibitors alone or in combination with pegilodecakin in patients with metastatic NSCLC (CYPRESS 1 and CYPRESS 2). J. Thorac. Oncol. 16, 327–333 (2021).
Liu, C. et al. mRNA-based cancer therapeutics. Nat. Rev. Cancer 23, 526–543 (2023).
Hewitt, S. L. et al. Durable anticancer immunity from intratumoral administration of IL-23, IL-36γ, and OX40L mRNAs. Sci. Transl. Med. 11, eaat9143 (2019).
Etxeberria, I. et al. Intratumor adoptive transfer of IL-12 mRNA transiently engineered antitumor CD8+ T cells. Cancer Cell 36, 613–629.e617 (2019).
Liu, J. Q. et al. Intratumoral delivery of IL-12 and IL-27 mRNA using lipid nanoparticles for cancer immunotherapy. J. Control. Release 345, 306–313 (2022).
Hotz, C. et al. Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models. Sci. Transl. Med. 13, eabc7804 (2021).
Li, W. et al. Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy. Nat. Commun. 12, 7264 (2021).
Kong, N. et al. Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes p53-deficient cancers to mTOR inhibition. Sci. Transl. Med. 11, eaaw1565 (2019).
Kong, N. et al. Intravesical delivery of KDM6A-mRNA via mucoadhesive nanoparticles inhibits the metastasis of bladder cancer. Proc. Natl Acad. Sci. USA 119, e2112696119 (2022).
Huang, X. et al. Synthesis of siRNA nanoparticles to silence plaque-destabilizing gene in atherosclerotic lesional macrophages. Nat. Protoc. 17, 748–780 (2022).
Islam, M. A. et al. Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA. Nat. Biomed. Eng. 2, 850–864 (2018).
Sun, Q. et al. STAT3 regulates CD8+ T cell differentiation and functions in cancer and acute infection. J. Exp. Med. 220, e20220686 (2023).
Brown, Z. J., Heinrich, B. & Greten, T. F. Mouse models of hepatocellular carcinoma: an overview and highlights for immunotherapy research. Nat. Rev. Gastroenterol. Hepatol. 15, 536–554 (2018).
Brown, Z. J., Heinrich, B. & Greten, T. F. Establishment of orthotopic liver tumors by surgical intrahepatic tumor injection in mice with underlying non-alcoholic fatty liver disease. Methods Protoc. 1, 21 (2018).
Zhu, A. X. et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 19, 940–952 (2018).
El-Khoueiry, A. B. et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 389, 2492–2502 (2017).
Yau, T. et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the CheckMate 040 randomized clinical trial. JAMA Oncol. 6, e204564 (2020).
Oshi, M. et al. Abstract 2072: DNA repair pathway score is associated with cancer aggressiveness and worse survival in hepatocellular carcinoma (HCC). Cancer Res. 81, 2072 (2021).
Chen, K.-S. et al. Bifunctional cancer cell–based vaccine concomitantly drives direct tumor killing and antitumor immunity. Sci. Transl. Med. 15, eabo4778 (2023).
Kanaya, N. et al. Gene-edited and -engineered stem cell platform drives immunotherapy for brain metastatic melanomas. Sci. Transl. Med. 15, eade8732 (2023).
Li, X. et al. Cancer immunotherapy based on image-guided STING activation by nucleotide nanocomplex-decorated ultrasound microbubbles. Nat. Nanotechnol. 17, 891–899 (2022).
Interleukin-2 wins FDA market clearance. Chem. Eng. News Archive 70, 5 (1992).
Ouyang, W. & O’Garra, A. IL-10 family cytokines IL-10 and IL-22: from basic science to clinical translation. Immunity 50, 871–891 (2019).
Saxton, R. A., Glassman, C. R. & Garcia, K. C. Emerging principles of cytokine pharmacology and therapeutics. Nat. Rev. Drug Discov. 22, 21–37 (2023).
Berraondo, P. et al. Cytokines in clinical cancer immunotherapy. Br. J. Cancer 120, 6–15 (2019).
Kon, E., Ad-El, N., Hazan-Halevy, I., Stotsky-Oterin, L. & Peer, D. Targeting cancer with mRNA-lipid nanoparticles: key considerations and future prospects. Nat. Rev. Clin. Oncol. 20, 739–754 (2023).
Chen, S. et al. Nanotechnology-based mRNA vaccines. Nat. Rev. Methods Prim. 3, 63 (2023).
Liu, S. et al. Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR-Cas gene editing. Nat. Mater. 20, 701–710 (2021).
Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020).
Liu, M., Hu, S., Yan, N., Popowski, K. D. & Cheng, K. Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity. Nat. Nanotechnol. 19, 565–575 (2024).
Rotolo, L. et al. Species-agnostic polymeric formulations for inhalable messenger RNA delivery to the lung. Nat. Mater. 22, 369–379 (2023).
Tang, Z. et al. Inhaled mRNA nanoparticles dual-targeting cancer cells and macrophages in the lung for effective transfection. Proc. Natl Acad. Sci. USA 120, e2304966120 (2023).
McCauley, S., Verma, R. & Oft, M. Pegilodecakin, a pegylated human IL-10 (AM0010), enhances the cytotoxicity of CAR-T cells in vitro and in vivo. Blood 132, 2058 (2018).
Li, Y. et al. Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity. Nat. Cancer 1, 882–893 (2020).
Zhang, Y. et al. Close the cancer-immunity cycle by integrating lipid nanoparticle-mRNA formulations and dendritic cell therapy. Nat. Nanotechnol. 18, 1364–1374 (2023).
Yang, J. et al. Intratumoral delivered novel circular mRNA encoding cytokines for immune modulation and cancer therapy. Mol. Ther. Nucleic Acids 30, 184–197 (2022).
Qu, L. et al. Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell 185, 1728–1744.e1716 (2022).
Chen, R. et al. Engineering circular RNA for enhanced protein production. Nat. Biotechnol. 41, 262–272 (2023).
Feng, Z. et al. An in vitro-transcribed circular RNA targets the mitochondrial inner membrane cardiolipin to ablate EIF4G2+/PTBP1+ pan-adenocarcinoma. Nat. Cancer 5, 30–46 (2023).
Huang, X. et al. The landscape of mRNA nanomedicine. Nat. Med. 28, 2273–2287 (2022).
Chen, S. et al. Nanotechnology-based mRNA vaccines. Nat. Rev. Methods Primers 3, 63 (2023).
Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37, 907–915 (2019).
La Ferlita, A. et al. RNAdetector: a free user-friendly stand-alone and cloud-based system for RNA-Seq data analysis. BMC Bioinform. 22, 298 (2021).
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
Mootha, V. K. et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273 (2003).
Ge, S. X., Jung, D. & Yao, R. ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics 36, 2628–2629 (2020).
