New Bacterial Immunotherapy Targets Solid Tumors
Researchers have unveiled ACTM-838, a novel, systemically delivered bacterial immunotherapy designed to enrich solid tumors with immune-stimulating payloads. Published in Volume 16 of Oncotarget on October 6, 2025, the study demonstrates how a specially engineered Salmonella Typhimurium strain can safely localize to tumors and deliver potent immune activators directly within the tumor microenvironment (TME). This approach aims to convert immune-suppressive TMEs into immune-permissive ones, enabling the body’s own defenses to combat cancer where many therapies fall short.
How ACTM-838 Works
ACTM-838 is built on a modular, live-attenuated bacterial platform optimized for tissue-specific localization and targeted payload delivery. By invading phagocytic cells within the TME, the therapy delivers two key immune-activating components: IL-15 bound to its receptor IL-15Rα, and a modified version of the stimulator of interferon genes (STING). The combined action of these signals enhances both innate and adaptive immune responses, shifting the balance within the tumor away from immune suppression and toward robust anti-tumor activity.
IL-15/IL-15Rα and STING: A Dual-Action Immune Push
IL-15 is a cytokine known for promoting the survival and activity of cytotoxic T-cells and natural killer (NK) cells. Delivering IL-15/IL-15Rα within the tumor helps amplify immune cell priming and persistence at the tumor site. The engineered STING payload further activates innate immune pathways, amplifying type I interferon signaling and antigen presentation. Together, these signals coordinate to mobilize both arms of the immune system, increasing the likelihood of durable tumor control.
Safety and Specificity in Tumor Targeting
A critical advancement reported in the Oncotarget paper is ACTM-838’s improved safety profile. The team demonstrates that the Salmonella Typhimurium strain is threadfully engineered to selectively localize within tumor tissue after intravenous administration, while minimizing exposure to healthy tissue. Notably, inflammatory toxicity was markedly reduced compared with the parent bacterial strain, addressing a major hurdle in previous bacterial therapies.
Preclinical Evidence of Efficacy
In murine models, ACTM-838 not only shrank established tumors but also reduced recurrence after treatment discontinuation. Cured mice resisted re-challenge with cancer cells, indicating the development of long-lasting immune memory. The therapy also showed strong synergy with anti-PD1 therapy, a widely used immune checkpoint inhibitor. This combination boosted anti-tumor responses in both treatment-resistant and responsive tumor models, suggesting ACTM-838 could extend the reach of existing immunotherapies.
Immune Landscape Remodeling in the Tumor
Analyses of the TME revealed meaningful shifts in immune cell populations. ACTM-838 increased cytotoxic T-cells and antigen-presenting macrophages, while reducing immunosuppressive cells such as regulatory T-cells and exhausted T-cells. These changes reflect a coordinated reboot of anti-tumor immunity, driven by the delivered IL-15/IL-15Rα and STING payloads. The genetic and cellular data support a mechanism whereby the therapy primes durable, multi-faceted immune responses against cancer cells.
Clinical Outlook and Future Directions
With ACTM-838 advancing into a Phase I clinical trial, the approach represents a promising new direction for treating solid tumors that are resistant to current immunotherapies. The concept of using live bacterial therapy to ferry gene-based immune modulators directly to tumors could unlock options for patients who have exhausted standard treatments. If successful, this strategy may augment existing therapies and pave the way for personalized, tumor-targeted immunotherapies that harness the body’s own defenses to achieve lasting remissions.
About the Study and Collaborators
The Oncotarget study is led by first author Kyle R. Cron with corresponding author Akshata R. Udyavar, and conducted by researchers from Actym Therapeutics. Their findings illuminate the potential of ATCM-838 as a safe, effective vehicle for delivering immune payloads to the TME and stimulating a durable anti-tumor immune response.
