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Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05538624\">NCT05538624<\/jats:ext-link>\n                      ) to identify Tpex recruitment capabilities at tolerable cytokine doses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show IL-12 cytokine factories can effectively treat a broad spectrum of cancer types. Single-cell RNA sequencing data suggests that the antitumor efficacy seen in our studies was due to retinal pigmented epithelial cells-mIL12 treatment inducing differentiation of Tpex cells within the tumor microenvironment. When administered in combination with checkpoint therapy, IL-12 cytokine factory treatment generated systemic abscopal immunity, preventing subcutaneous tumor outgrowth in 8\/9 mice with colorectal cancer and lung metastasis in mice with melanoma. Furthermore, this platform was well tolerated in a non-human primate without signs of toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our new immunotherapy approach provides a robust strategy for inducing Tpex recruitment and systemic immunity against a range of solid peritoneal malignancies, many incurable with current immunotherapy strategies. Notably, these features were achieved using IL-12, and by leveraging our technology, we avoided the toxicities that have prevented the translation of IL-12 to the clinic. Our findings provide a strong rationale for the clinical development of IL-12 cytokine factories.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2024-010685","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T17:21:14Z","timestamp":1743528074000},"page":"e010685","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["IL-12-producing cytokine factories induce precursor exhausted T cells and elimination of primary and metastatic tumors"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct05538624","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05538624","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05538624","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Amanda","family":"Nash","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Rice University, 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