Tumor-Colonizing E. coli Expressing Both Collagenase and Hyaluronidase Enhances Therapeutic Efficacy of Gemcitabine in Pancreatic Cancer Models.

Autor: Avsharian LC; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.; Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA 91010, USA., Loganathan S; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA., Ebelt ND; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA., Shalamzari AF; Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA 91010, USA., Rodarte Muñoz I; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA., Manuel ER; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2024 Nov 17; Vol. 14 (11). Date of Electronic Publication: 2024 Nov 17.
DOI: 10.3390/biom14111458
Abstrakt: Desmoplasia is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC) that contributes significantly to treatment resistance. Approaches to enhance drug delivery into fibrotic PDAC tumors continue to be an important unmet need. In this study, we have engineered a tumor-colonizing E. coli -based agent that expresses both collagenase and hyaluronidase as a strategy to reduce desmoplasia and enhance the intratumoral perfusion of anticancer agents. Overall, we observed that the tandem expression of both these enzymes by tumor-colonizing E. coli resulted in the reduced presence of intratumoral collagen and hyaluronan, which likely contributed to the enhanced chemotherapeutic efficacy observed when used in combination. These results highlight the importance of combination treatments involving the depletion of desmoplastic components in PDAC before or during treatment.
Databáze: MEDLINE
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