Effect of rabbit carboxylesterase conversion of prodrug CPT11 to SN38 on the survival of Glioma cells
Research has discovered the migratory capabilities of neural stem cells to tumor cells. The HB1.F3 CD (cytosine deaminase) multipotent neural stem cell line utilized in this research contains a retroviral insertion of the vmyc gene to maintain replication and stability during passage thereby immortalizing them. By engineering these cells to aid in the administration of anti-cancer drugs (Topoisomerase-1 or Top-1 inhibitors), more efficient means of treating highly ubiquitous and metastasizing tumors such as with Gliomas are in development. These neural stem cells are transduced with adenovirus rabbit carboxylesterase (rCE) so that in the presence of Top-1 inhibitor and camptothecin derivative, irinotecan (CPT11), initiation of its active form, SN38, occurs and higher grade killing is expected. Using a Cytotoxicity assay and Sulforhodamine B (SRB) assay the sensitivity of glioma cell lines D566 and U87 to CPT11 and SN-38 is measured contrasting the drugs? killing capacities. SN38 is too toxic to be administered directly in the body but efficient in its passing the blood brain barrier (when compared to less efficient prodrugs like CD). Thus, the stem cells merely secrete the rCE into their surrounding media which upon culture of 6 days is collected and utilized in converting the prodrug to SN38. Finally two other carboxylesterases MUT6 and NULL the humanized CEs paired with the rCE will be monitored for their affects on the growth of F3CDs.
Leong, Amanda, "Effect of rabbit carboxylesterase conversion of prodrug CPT11 to SN38 on the survival of Glioma cells" (2009). URC Student Scholarship.
Dr. Karen Aboody, City of Hope
Howard Hughes Medical Institute Undergraduate Science Education Grant