{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:56:00Z","timestamp":1791428160878,"version":"4.3.3"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Innovative Immune Alliance"},{"name":"French Embassy in Havana"},{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The main limitations of cancer treatment with high doses of recombinant interleukin 2 (IL-2) are high toxicity and the undesired expansion of regulatory T cells. The generation of IL-2 mutated variants (muteins) with changes in the affinity for different chains of the IL-2 receptor (IL-2R) allows selective stimulation of effector cells while overcoming its toxicity. As increasing the IL-2 affinity for the IL-2R beta chain leads to better antitumor effect, we generated a group of these muteins using phage display technology, in a previous work. Recombinant Fc-fusion proteins, including these variants, resulted in improved developability properties and better in vivo effect than variants containing the IL-2 (IL-2Fc). Here, we assessed one such improved mutein, named superbeta 834 (SB834Fc), and performed a comprehensive characterization of its properties. This mutein showed a stronger antitumor effect than IL-2Fc in 5 murine tumor models: 3LL-D122, B16F10, CT26, MC38, and 4T1 at very low doses. Different from other IL-2 variants, SB834Fc, as single therapy, shows antitumor effect in a therapeutic injection scheme. This antitumor effect was coincident with strong stimulation of effector T cells in the spleen and in the tumor microenvironment, far above that observed with IL-2Fc, despite maintaining the same level of Treg stimulation. Additionally, induction of proliferation was demonstrated in CD8+ T cells isolated from human healthy donors, highlighting its translational value. These results support the SB834Fc fusion protein as a suitable candidate to develop a new cancer immunotherapy based in IL-2.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf208","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T17:02:53Z","timestamp":1756400573000},"page":"3028-3042","source":"Crossref","is-referenced-by-count":2,"title":["Enhanced affinity for the IL-2 receptor \u03b2 subunit potently increases antitumor efficacy of IL-2 across various tumor models by reshaping the tumor microenvironment"],"prefix":"10.1093","volume":"214","author":[{"given":"Ernesto","family":"Relova-Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4573-6558","authenticated-orcid":false,"given":"Ana Beatriz","family":"D\u00edaz-Bravo","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Pedroso","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine , Lisbon,","place":["Portugal"]},{"name":"Faculdade de Medicina, Universidade de Lisboa , Lisbon,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"Gonzalez-Cruz","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliany","family":"Arias","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayana","family":"P\u00e9rez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rydell","family":"\u00c1lvarez-Arzola","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Avellanet","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisandra","family":"Padr\u00f3n","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Addys","family":"Gonz\u00e1lez Palomo","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Gra\u00e7a","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine , Lisbon,","place":["Portugal"]},{"name":"Faculdade de Medicina, Universidade de Lisboa , Lisbon,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalet","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertrudis","family":"Rojas","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-0035","authenticated-orcid":false,"given":"Tania","family":"Carmenate","sequence":"additional","affiliation":[{"name":"Center of Molecular Immunology , Havana, 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