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To achieve this, potent cellular adjuvants are highly needed. Interleukin-1\u03b2 (IL-1\u03b2) acts on CD8<jats:sup>+<\/jats:sup> T cells and promotes their expansion and effector differentiation, but toxicity and undesired tumor-promoting side effects hamper efficient clinical application of this cytokine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This \u2018cytokine problem\u2019 can be solved by use of AcTakines (<jats:underline>Ac<\/jats:underline>tivity-on-<jats:underline>Ta<\/jats:underline>rget cyto<jats:underline>kines<\/jats:underline>), which represent fusions between low-activity cytokine mutants and cell type-specific single-domain antibodies. AcTakines deliver cytokine activity to <jats:italic>a priori<\/jats:italic> selected cell types and as such evade toxicity and unwanted off-target side effects. Here, we employ subcutaneous melanoma and lung carcinoma models to evaluate the antitumor effects of AcTakines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this work, we use an IL-1\u03b2-based AcTakine to drive proliferation and effector functionality of antitumor CD8<jats:sup>+<\/jats:sup> T cells without inducing measurable toxicity. AcTakine treatment enhances diversity of the T cell receptor repertoire and empowers adoptive T cell transfer. Combination treatment with a neovasculature-targeted tumor necrosis factor (TNF) AcTakine mediates full tumor eradication and establishes immunological memory that protects against secondary tumor challenge. Interferon-\u03b3 was found to empower this AcTakine synergy by sensitizing the tumor microenvironment to TNF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our data illustrate that anticancer cellular immunity can be safely promoted with an IL-1\u03b2-based AcTakine, which synergizes with other immunotherapies for efficient tumor destruction.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2021-003293","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T11:30:21Z","timestamp":1636716621000},"page":"e003293","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Selective IL-1 activity on CD8<sup>+<\/sup> T cells empowers antitumor immunity and synergizes with neovasculature-targeted TNF for full tumor 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Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5443-7027","authenticated-orcid":false,"given":"Anje","family":"Cauwels","sequence":"additional","affiliation":[{"name":"VIB-UGent Center for Medical Biotechnology, Ghent, Belgium"},{"name":"Department of Biomolecular Medicine, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4150-5772","authenticated-orcid":false,"given":"Gilles","family":"Uz\u00e9","sequence":"additional","affiliation":[{"name":"IRMB, University Montpellier, INSERM, CNRS, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niko","family":"Kley","sequence":"additional","affiliation":[{"name":"Orionis Biosciences Inc, Waltham, Massachusetts, 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