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Eng"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immunosuppressive microenvironments, the lack of immune infiltration, and antigen heterogeneity pose challenges for chimaeric antigen receptor (CAR)-T cell therapies applied to solid tumours. Previously, CAR-T cells were armoured with immunostimulatory molecules, such as interleukin 12 (IL-12), to overcome this issue, but faced high toxicity. Here we show that collagen-binding domain-fused IL-12 (CBD-IL-12) secreted from CAR-T cells to target human six transmembrane epithelial antigen of prostate 1 (STEAP1) is retained within murine prostate tumours. This leads to high intratumoural interferon-\u03b3 levels, without hepatotoxicity and infiltration of T cells into non-target organs compared with unmodified IL-12. Both innate and adaptive immune compartments are activated and recognize diverse tumour antigens after CBD-IL-12-armoured CAR-T cell treatment. A combination of CBD-IL-12-armoured CAR-T cells and immune checkpoint inhibitors eradicated large tumours in an established prostate cancer mouse model. In addition, human CBD-IL-12-armoured CAR-T cells showed potent anti-tumour efficacy in a 22Rv1 xenograft while reducing circulating IL-12 levels compared with unmodified IL-12-armoured CAR-T cells. CBD fusion to potent payloads for CAR-T therapy may remove obstacles to their clinical translation towards elimination of solid tumours.<\/jats:p>","DOI":"10.1038\/s41551-025-01508-3","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:02:07Z","timestamp":1761177727000},"page":"630-646","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Collagen-binding IL-12-armoured STEAP1 CAR-T cells reduce toxicity and treat prostate cancer in mouse models"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9966-957X","authenticated-orcid":false,"given":"Koichi","family":"Sasaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul","family":"Bhatia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4720-2238","authenticated-orcid":false,"given":"Yuta","family":"Asano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1602-5231","authenticated-orcid":false,"given":"Jakob","family":"Bakhtiari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9876-5800","authenticated-orcid":false,"given":"Takumi","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Dubois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Chuan","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donny","family":"Gun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charanjit","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Panagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurine","family":"Noblecourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7196-2707","authenticated-orcid":false,"given":"Maria","family":"Nikolaidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Truman","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Javier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8136-2112","authenticated-orcid":false,"given":"Saul J.","family":"Priceman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude G.","family":"Chapuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6570-2180","authenticated-orcid":false,"given":"John K.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9083-9859","authenticated-orcid":false,"given":"Jun","family":"Ishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"1508_CR1","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1056\/NEJMoa1407222","volume":"371","author":"SL Maude","year":"2014","unstructured":"Maude, S. 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NCBI GEO https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE300750 (2025)."}],"container-title":["Nature Biomedical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41551-025-01508-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-025-01508-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-025-01508-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:02:16Z","timestamp":1776834136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41551-025-01508-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":54,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["1508"],"URL":"https:\/\/doi.org\/10.1038\/s41551-025-01508-3","relation":{},"ISSN":["2157-846X"],"issn-type":[{"value":"2157-846X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]},"assertion":[{"value":"18 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"K.S., Y.A., A.G.C., J.K.L. and J.I. are inventors on a US provisional patent application (No. 63\/650,382) covering the technology described in this work. K.S. and J.I. are inventors on international patent applications (PCT\/US2019\/020685) covering CBD-IL-12 protein therapy. J.K.L. is an inventor on international patent applications (PCT\/US2023\/062428) related to STEAP1 CAR-T cells. J.K.L. holds equity in, serves on the scientific advisory board of, and receives research funding from PromiCell Therapeutics. J.K.L. is a consultant for Lyell Immunopharma. J.I. is a founder and shareholder in Arrow Immune Inc. J.I. is a scientific advisor of EsoBiotec. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}