A new research paper was published in\u00a0Volume 16 of\u00a0Oncotarget\u00a0on October 6, 2025, titled “ACTM-838, a novel systemically delivered bacterial immunotherapy that enriches in solid tumors and delivers IL-15\/IL-15R\u03b1 and STING payloads to engage innate and adaptive immunity in the TME and enable a durable anti-tumor immune response.”<\/p>\n
In this study, led by first author Kyle R. Cron and corresponding author Akshata R. Udyavar, researchers from\u00a0Actym Therapeutics\u00a0developed a new form of bacterial immunotherapy<\/a> called ACTM-838. This treatment safely delivers immune-activating proteins directly to solid tumors. The approach may offer a new option for cancer patients whose solid tumors are resistant to current immunotherapies.<\/p>\n Solid tumors often suppress the immune system, making it difficult for treatments like immune checkpoint inhibitors to work effectively. ACTM-838 was designed to overcome this challenge by targeting phagocytic immune cells within the tumor microenvironment (TME). Once inside the tumor, the therapy delivers two immune-stimulating components: IL-15\/IL-15R\u03b1 and a modified version of STING. Both are known to activate the body’s innate and adaptive immune responses. This combination of immune-stimulating proteins helps shift the TME from immune-suppressive to immune-permissive, enabling the body’s natural defenses to fight the cancer.<\/p>\n “STACT is a modular, genetically engineered live attenuated S. Typhimurium bacterial platform that enables tissue-specific localization and cell-targeted delivery of large, multiplexed payloads via systemic administration.”<\/p>\n The study highlights how ACTM-838, built on a specially modified strain of\u00a0Salmonella Typhimurium, safely targets tumors and avoids healthy tissue after intravenous injection. This targeted delivery reduces the risk of side effects while ensuring the immune-boosting agents reach their intended location. Importantly, ACTM-838 also showed significantly reduced inflammatory toxicity compared to its parent bacterial strain, which had previously presented challenges in clinical use.<\/p>\n In preclinical tests, ACTM-838 shrank tumors and prevented their recurrence after treatment. Mice that were cured of tumors resisted re-injection with cancer cells, suggesting the development of long-lasting immune memory. The therapy also showed strong synergy with anti-PD1 drugs, a widely used class of cancer treatments, further improving outcomes in both treatment-resistant and responsive tumor models.<\/p>\n Researchers also found that ACTM-838 changed the composition of immune cells within the tumor. It increased beneficial cells like cytotoxic T-cells and antigen<\/a>-presenting macrophages, while reducing suppressive cell types such as regulatory T-cells and exhausted T-cells. These effects were confirmed through genetic analysis and cellular studies, pointing to a broad and coordinated immune response.<\/p>\n This study offers proof-of-concept that live bacterial therapy can safely and effectively deliver gene-based immune modulators directly to tumors. With ACTM-838 now being tested in a Phase I clinical trial, the findings offer a new direction for cancer treatment strategies that activate the body’s own immune system, particularly in difficult-to-treat cases where other therapies fail.<\/p>\n Source:<\/p>\n Journal reference:<\/p>\n Cron, K. R., et al. (2025). ACTM-838, a novel systemically delivered bacterial immunotherapy that enriches in solid tumors and delivers IL-15\/IL-15R\u03b1 and STING payloads to engage innate and adaptive immunity in the TME and enable a durable anti-tumor immune response.\u00a0Oncotarget. doi.org\/10.18632\/oncotarget.28769<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"A new research paper was published in\u00a0Volume 16 of\u00a0Oncotarget\u00a0on October 6, 2025, titled “ACTM-838, a novel systemically delivered…\n","protected":false},"author":2,"featured_media":2534,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[16943,258,3169,19296,1241,103,61,22005,3176,3177,8267,60,10221,3063,13251,16323,89,3067],"class_list":["post-67338","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-bacterial","tag-cancer","tag-cell","tag-efficacy","tag-genes","tag-health","tag-ie","tag-immune-response","tag-immune-system","tag-immunity","tag-immunotherapy","tag-ireland","tag-neutrophils","tag-oncology","tag-preclinical","tag-reproduction","tag-research","tag-tumor"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/67338","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=67338"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/67338\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/2534"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=67338"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=67338"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=67338"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}