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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
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CMTM6-Silencing Microbial Immunotherapy Reprograms PDAC Tumors and Restores T-cell Function
C Y Chabu1, R Kazmierczak1, M Hasani1
1Division of Biological Sciences, University of Missouri, Columbia, MO, 65211.
Biorxiv : the Preprint Server for Biology
|February 9, 2026
Summary
This study introduces iSTORM, a novel microbial immunotherapy that targets pancreatic cancer (PDAC) by colonizing tumors and enhancing anti-tumor immune responses. iSTORM demonstrates improved T-cell activation and tumor control, offering a promising new treatment strategy for PDAC.
Area of Science:
- Microbial immunotherapy
- Oncology
- Immunology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is largely resistant to current immunotherapies.
- Dense fibrosis and immune suppression limit T-cell infiltration in PDAC.
- Previous attenuated Salmonella strains showed limited efficacy and safety concerns.
Purpose of the Study:
- To evaluate the tumor-targeting, immune remodeling, and safety profiles of CRC2631 and its derivative iSTORM for PDAC treatment.
- To engineer a next-generation microbial therapy for enhanced anti-tumor immunity in PDAC.
Main Methods:
- Utilized attenuated Salmonella enterica serovar Typhimurium strain CRC2631 and its derivative iSTORM.
- Assessed tumor colonization, immune cell infiltration, and transcriptional changes in PDAC models.
- Investigated CMTM6 silencing and its effect on PD-L1 expression and T-cell activation.
- Conducted toxicity studies to evaluate the safety profile of iSTORM.
Main Results:
- CRC2631 and iSTORM preferentially colonized PDAC tumors.
- iSTORM enhanced intratumoral CD8+ T cells and promoted T-cell activation.
- iSTORM demonstrated deeper tumor control compared to CRC2631.
- Lyophilized iSTORM formulation preserved immune remodeling and improved deployability.
- iSTORM exhibited a favorable safety profile in toxicity studies.
Conclusions:
- iSTORM is a safe and effective microbial immunotherapy platform for PDAC.
- iSTORM selectively targets PDAC tumors, remodels the tumor microenvironment, and unleashes anti-tumor immune activity.
- The glycan-guided, CMTM6-targeted bacterial platform holds potential for scalable PDAC treatment and other immunologically cold tumors.
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