{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:53:14Z","timestamp":1791337994583,"version":"4.3.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>This study investigated the safety and therapeutic potential of recombinant canine interleukin-15 (rcIL-15) as an adjunct to surgical excision in dogs with mammary gland tumors (MGTs). Sixty-one client-owned dogs were initially enrolled, and 55 completed the 12-week study. Dogs were assigned to a test group receiving rcIL-15 with surgery or a control group undergoing surgery alone. RcIL-15 was administered intravenously at 20\u202f\u03bcg\/kg\/day for two 4-day\u202fcycles, separated by a 10-day rest period. Clinical monitoring included physiological assessments, blood tests, and owner-reported quality of life (QoL) questionnaires. No significant adverse changes were observed in hematological, biochemical, or physiological parameters. RcIL-15 was well tolerated, with only mild and self-limiting gastrointestinal signs and injection site reactions. Dogs in the rcIL-15 group showed significantly improved QoL, particularly in pain, appetite, and activity. Notably, serum C-reactive protein levels decreased over time in the rcIL-15 group, suggesting reduced systemic inflammation. VEGF levels remained stable in the test group but increased in controls, while IFN-<jats:italic>\u03b3<\/jats:italic> concentrations rose significantly following rcIL-15 treatment, indicating immune activation. These findings suggest that rcIL-15 may enhance antitumor immunity and alleviate tumor-related inflammation without compromising safety. The combination of surgery and rcIL-15 improved clinical outcomes compared to surgery alone, supporting its use as a novel immunotherapeutic adjunct for canine MGTs. However, limitations include the short follow-up period and lack of cellular immune profiling. Further studies with longer follow-up and immunological assessment are warranted to confirm these results and explore the broader application of rcIL-15 in veterinary oncology.<\/jats:p>","DOI":"10.3389\/fvets.2025.1603421","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T13:50:46Z","timestamp":1749477046000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Safety and efficacy of canine recombinant IL-15 in mammary gland tumors"],"prefix":"10.3389","volume":"12","author":[{"given":"Min-Hee","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeil","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Ki","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeyoung","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Ae","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Myung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e0127381","DOI":"10.1371\/journal.pone.0127381","article-title":"Epidemiological study of mammary tumors in female dogs diagnosed during the period 2002-2012","volume":"10","author":"Salas","year":"2015","journal-title":"PLoS One"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/s0195-5616(03)00020-2","article-title":"Canine mammary gland tumors","volume":"33","author":"Sorenmo","year":"2003","journal-title":"Vet Clin Small Anim"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e0302231","DOI":"10.1371\/journal.pone.0302231","article-title":"Incidence rates of the most common canine tumors based on data from the Swiss canine Cancer registry (2008 to 2020)","volume":"19","author":"Dhein","year":"2024","journal-title":"PLoS One"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13028-023-00674-1","article-title":"Surgical dose and the clinical outcome in the treatment of mammary gland tumors in female dogs: a literature review","volume":"65","author":"H\u00f6rnfeldt","year":"2023","journal-title":"Acta Vet Scand"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"232","DOI":"10.29261\/pakvetj\/2023.037","article-title":"Anatomical and histopathological comparative studies between right and left mammary tumors in a rat model induced by DMBA","volume":"43","author":"Maaruf","year":"2023","journal-title":"Pak Vet J"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s13028-015-0121-3","article-title":"Surgical stress and postoperative complications related to regional and radical mastectomy in dogs","volume":"24","author":"Horta","year":"2015","journal-title":"Acta Vet Scand"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1111\/vco.12092","article-title":"Surgical treatment of mammary carcinomas in dogs with or without postoperative chemotherapy","volume":"14","author":"Tran","year":"2016","journal-title":"Vet Comp Oncol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1111\/j.1532-950X.2007.00351.x","article-title":"Mammary tumor recurrence in bitches after regional mastectomy","volume":"37","author":"Stratmann","year":"2008","journal-title":"Vet Surg"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1184703","DOI":"10.3389\/fphar.2023.1184703","article-title":"Research progress of interleukin-15 in cancer immunotherapy","volume":"14","author":"Cai","year":"2023","journal-title":"Front Pharmacol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.2174\/0118715206321574240821112747","article-title":"Immunomodulatory roles of IL-15 in immune cells and its potential for cancer immunotherapy","volume":"24","author":"Liu","year":"2024","journal-title":"Anti Cancer Agents Med Chem"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"107318","DOI":"10.1016\/j.intimp.2020.107318","article-title":"Biological effects of IL-15 on immune cells and its potential for the treatment of cancer","volume":"91","author":"Zhang","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"155599","DOI":"10.1016\/j.cyto.2021.155599","article-title":"Safety and immunological effects of recombinant canine IL-15 in dogs","volume":"148","author":"Lee","year":"2021","journal-title":"Cytokine"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vetimm.2015.04.002","article-title":"Generation of recombinant canine interleukin-15 and evaluation of its effects on the proliferation and function of canine NK cells","volume":"165","author":"Lee","year":"2015","journal-title":"Vet Immunol Immunopathol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"755","DOI":"10.5455\/OVJ.2021.v11.i4.28","article-title":"Quality of life assessment in cancer patients receiving single-agent versus multidrug chemotherapy protocols","volume":"11","author":"Bianchi","year":"2021","journal-title":"Open Vet J"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/vco.12677","article-title":"Veterinary cooperative oncology group-common terminology criteria for adverse events (VCOG-CTCAE v2) following investigational therapy in dogs and cats","volume":"19","author":"LeBlanc","year":"2021","journal-title":"Vet Comp Oncol"},{"key":"ref16","first-page":"318","article-title":"Clinical staging in bitches with mammary tumors: influence of type and histological grade","volume":"80","author":"Gundim","year":"2016","journal-title":"Can J Vet Res"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1111\/j.1939-1676.2003.tb02522.x","article-title":"The utility of plasma D-dimer to identify thromboembolic disease in dogs","volume":"17","author":"Nelson","year":"2003","journal-title":"J Vet Intern Med"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1111\/j.1939-165X.2009.00139.x","article-title":"Evaluation of serum haptoglobin and C-reactive protein in dogs with mammary tumors","volume":"38","author":"Planellas","year":"2009","journal-title":"Vet Clin Pathol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"110923","DOI":"10.1016\/j.vetimm.2025.110923","article-title":"Evaluation of clinical and immunological responses to recombinant canine interleukin-15 therapy in dogs with cancer: a pilot study","volume":"283","author":"Lim","year":"2025","journal-title":"Vet Immunol Immunopathol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"824982","DOI":"10.3389\/fvets.2022.824982","article-title":"Clinical and serological hallmarks of cytokine release syndrome in a canine B cell lymphoma patient treated with autologous CAR-T cells","volume":"9","author":"Atherton","year":"2022","journal-title":"Front Vet Sci"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1111\/jvim.15852","article-title":"Autologous cancer cell vaccination, adoptive T cell transfer, and interleukin-2 administration in dogs with osteosarcoma","volume":"34","author":"Flesner","year":"2020","journal-title":"J Vet Intern Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1111\/j.1476-5829.2010.00244.x","article-title":"Development of a questionnaire assessing health-related quality-of-life in dogs and cats with cancer","volume":"9","author":"Lynch","year":"2011","journal-title":"Vet Comp Oncol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e0143080","DOI":"10.1371\/journal.pone.0143080","article-title":"C-reactive protein is an important biomarker for prognosis, tumor recurrence and treatment response in adult solid tumors: a systematic review","volume":"10","author":"Shrotriya","year":"2015","journal-title":"PLoS One"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.14202\/vetworld.2022.2810-2815","article-title":"Impact of serum c-reactive protein level as a biomarker of cancer dissemination in canine lymphoid neoplasia","volume":"15","author":"Manachai","year":"2022","journal-title":"Vet World"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.tips.2011.09.004","article-title":"Interleukin-15 biology and its therapeutic implications in cancer","volume":"33","author":"Steel","year":"2012","journal-title":"Trends Pharmacol Sci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3586","DOI":"10.3390\/cancers12123586","article-title":"Immunomodulatory effects of IL-2 and IL-15: implications for cancer immunotherapy","volume":"12","author":"Yang","year":"2020","journal-title":"Cancers (Basel)"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1354\/vp.39-4-488","article-title":"Expression of vascular endothelial growth factor in canine mammary tumors","volume":"39","author":"Restucci","year":"2002","journal-title":"Vet Pathol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"6977","DOI":"10.4049\/jimmunol.161.12.6977","article-title":"Combination chemotherapy and IL-15 administration induce permanent tumor regression in a mouse lung tumor model: NK and T cell-mediated effects antagonized by B cells","volume":"161","author":"Chapoval","year":"1998","journal-title":"J Immunol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e004645","DOI":"10.1136\/jitc-2022-004493","article-title":"Inhaled recombinant human interleukin-15 in dogs with pulmonary metastases from osteosarcoma or melanoma: a phase I study","volume":"10","author":"Rebhun","year":"2022","journal-title":"J Immunother Cancer"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1603421\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T13:50:48Z","timestamp":1749477048000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1603421\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":29,"alternative-id":["10.3389\/fvets.2025.1603421"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2025.1603421","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"article-number":"1603421"}}