Engineered probiotic <i>Bifidobacterium</i> for tumor-targeted pancreatic cancer therapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42490449.
- Also identified by DOI 10.1126/sciadv.adz1388.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) presents a substantial challenge due to its resistance to cancer treatments. This limited efficacy is, in part, attributed to the immunosuppressive tumor microenvironment (TME), which impairs effector T (T<sub>eff</sub>) cell activity. Interleukin-2 (IL-2) is a key cytokine for T cell activation, but its therapeutic use is limited by a short half-life, systemic toxicity, and regulatory T (T<sub>reg</sub>) activation. To address this limitation, we engineered <i>Bifidobacterium longum</i>, a probiotic obligate anaerobe that selectively colonizes the TME, to continuously secrete Super-mutant IL-2 (SumIL-2), an engineered IL-2 variant that preferentially activates T<sub>eff</sub> cells over T<sub>reg</sub> cells, thereby delivering SumIL-2 selectively to the tumor (BifidoSumIL-2). Systemic administration of BifidoSumIL-2 significantly suppressed tumor growth in both subcutaneous tumors and orthotopic PDAC in mice, inducing an improved T<sub>eff</sub>/T<sub>reg</sub> ratio. Combining BifidoSumIL-2 with chemotherapy, radiation, and immunotherapy further restrained orthotopic PDAC growth, highlighting its therapeutic potential for difficult-to-treat cancers like PDAC.
Medical subject headings
- Probiotics
- Pancreatic Neoplasms
- Interleukin-2
- Bifidobacterium
- Carcinoma, Pancreatic Ductal