Related Experiment Video
Updated: Jul 30, 2026
Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
Published on: September 10, 2014
Peritoneal cancer treatment with CYP2B1 transfected, microencapsulated cells and ifosfamide
1Department of Surgery, University Hospital Mannheim, University of Heidelberg, Germany. stephan.samel@web.de
Abstract:
The prognosis of peritoneal spread from gastrointestinal cancer and subsequent malignant ascites is poor, and current medical treatments available are mostly ineffective. Targeted chemotherapy with intraperitoneal prodrug activation may be a beneficial new approach. L293 cells were genetically modified to express the cytochrome P450 enzyme 2B1 under the control of a cytomegalovirus immediate early promoter. This CYP2B1 enzyme converts ifosfamide to its active cytotoxic compounds. The cells are encapsulated in a cellulose sulfate formulation (Capcell). Adult Balb/c mice were inoculated intraperitoneally with 1 x 10(6) colon 26 cancer cells, previously transfected with GFP to emit a stable green fluorescence, by injection into the left lower abdominal quadrant. Two or five day's later animals were randomly subjected to either i.p. treatment with ifosfamide alone or ifosfamide combined with microencapsulated CYP2B1-expressing cells. Peritoneal tumor volume and tumor viability were assessed 10 days after tumor inoculation by means of fluorescence microscopy, spectroscopy and histology. Early i.p. treatment with ifosfamide and CYP2B1 cells resulted in a complete response. Treatment starting on day 5 and single-drug treatment with ifosfamide resulted in a partial response. These results suggest that targeted i.p. chemotherapy using a combination of a prodrug and its converting enzyme may be a successful treatment strategy for peritoneal spread from colorectal cancer.
Insights
Targeted intraperitoneal chemotherapy using microencapsulated cells expressing cytochrome P450 2B1 (CYP2B1) enzyme effectively treats peritoneal spread from gastrointestinal cancer. This approach converts ifosfamide into active compounds, showing complete response in early treatment models.
Area of Science:
- Oncology
- Cancer Therapy
- Biotechnology
Background:
- Peritoneal spread from gastrointestinal cancer and malignant ascites have a poor prognosis with limited effective treatments.
- Targeted chemotherapy using intraperitoneal prodrug activation presents a potential novel therapeutic strategy.
Purpose of the Study:
- To evaluate the efficacy of genetically modified cells expressing cytochrome P450 2B1 (CYP2B1) for targeted intraperitoneal chemotherapy.
- To assess the treatment of peritoneal carcinomatosis using microencapsulated CYP2B1-expressing cells and ifosfamide in a murine model.
Main Methods:
- L293 cells were engineered to express CYP2B1 under a CMV promoter and encapsulated in Capcell.
- Murine model of peritoneal carcinomatosis established using GFP-transfected colon 26 cancer cells.
- Animals received intraperitoneal treatment with ifosfamide alone or combined with microencapsulated CYP2B1-expressing cells at different time points.
Main Results:
- Early intraperitoneal treatment with ifosfamide and CYP2B1-expressing cells achieved a complete response.
- Delayed treatment (day 5) and ifosfamide monotherapy resulted in a partial response.
- Tumor volume and viability were significantly reduced with the combined early treatment approach.
Conclusions:
- Targeted intraperitoneal chemotherapy combining a prodrug with its converting enzyme is a promising strategy for peritoneal spread of colorectal cancer.
- The use of microencapsulated CYP2B1-expressing cells offers a localized and potentially more effective cancer treatment modality.
- Further research into this approach could lead to improved outcomes for patients with advanced gastrointestinal malignancies.
More Related Videos
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:27Tumor Immunotherapy