Targeted intraabdominal chemotherapy for peritoneal carcinomatosis

Area of Science:

• Oncology
• Cancer Therapy
• Drug Delivery Systems

Background:

• Peritoneal spread from gastrointestinal cancer leads to malignant ascites with a poor prognosis and limited effective treatments.
• Targeted chemotherapy with intraperitoneal prodrug activation presents a potential novel therapeutic avenue.

Purpose of the Study:

• To evaluate the efficacy of genetically modified cells expressing cytochrome P450 2B1 (CYP2B1) for targeted intraperitoneal chemotherapy.
• To establish and utilize a reproducible mouse model for metastatic peritoneal cancer to assess treatment response.

Main Methods:

• L293 cells were engineered to express CYP2B1 and encapsulated in Capcell.
• Mice were inoculated with GFP-transfected colon cancer cells and treated with ifosfamide alone or in combination with CYP2B1-expressing cells.
• Tumor volume and viability were assessed using fluorescence microscopy, spectroscopy, and histology.

Main Results:

• Early treatment with ifosfamide and CYP2B1-expressing cells achieved a complete response in peritoneal tumors.
• Delayed treatment or ifosfamide monotherapy resulted in a partial response.
• The intraperitoneal administration of Capcell and ifosfamide was well-tolerated in the animal model.

Conclusions:

• Targeted intraperitoneal chemotherapy combining a prodrug with its converting enzyme is a potentially successful strategy for peritoneal spread of colorectal cancer.
• The developed GFP-transfected colon cancer mouse model is effective for evaluating treatment responses in metastatic peritoneal cancer.
• This method allows for specific targeting of chemotherapeutic agents to peritoneal metastatic sites.