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Following injection, near-infrared light activates the conjugate causing direct cytotoxicity and immunogenic cell death. The high selectivity of NIR-PIT is traditionally based on the binding of a monoclonal antibody to its target thus bringing the photoabsorber, IR700, in close proximity to the cell membrane at the time of light exposure. However, other targeting moieties can be used and in the current study, interleukin-15 (IL15) is conjugated with IR700 to enable NIR-PIT. IL15-IR700 quickly bound to the cellular membrane of MC38 HIL15R\u03b1 cells that are transfected with human IL15 receptor alpha. NIR-PIT induced characteristic morphological changes accompanied by a significant decrease of cellular viability. Intratumoral injection of IL15-IR700 resulted in longer retention of the conjugate in the tumor compared to the intravenous injection. NIR-PIT with intratumoral IL15-IR700 significantly suppressed tumor growth, induced necrosis-like changes in tumor tissue, and stimulated host immune response. This study revealed that cytokine-based NIR-PIT is a potential therapeutic strategy for treating solid cancer.<\/jats:p>","DOI":"10.1007\/s00262-025-04151-8","type":"journal-article","created":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T07:35:15Z","timestamp":1756625715000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interleukin 15 (IL15)-based near-infrared photoimmunotherapy"],"prefix":"10.1007","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0348-9422","authenticated-orcid":false,"given":"Motofumi","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-4219","authenticated-orcid":false,"given":"Aki","family":"Furusawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyu","family":"Kano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7920-0763","authenticated-orcid":false,"given":"Seiichiro","family":"Takao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Okuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1086-8826","authenticated-orcid":false,"given":"Peter L.","family":"Choyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1019-4112","authenticated-orcid":false,"given":"Hisataka","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"4151_CR1","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1038\/nm.2554","volume":"17","author":"M Mitsunaga","year":"2011","unstructured":"Mitsunaga M, Ogawa M, Kosaka N, Rosenblum LT, Choyke PL, Kobayashi H (2011) Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. 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