title: Development of a tumor-selective approach to treat metastatic cancer.
abstract: BACKGROUND
  Patients diagnosed with metastatic cancer have almost uniformly poor prognoses. The treatments available for patients with disseminated disease are usually not curative and have side effects that limit the therapy that can be given. A treatment that is selectively toxic to tumors would maximize the beneficial effects of therapy and minimize side effects, potentially enabling effective treatment to be administered.
  
  
  RESULTS
  We postulated that the tumor-tropic property of stem cells or progenitor cells could be exploited to selectively deliver a therapeutic gene to metastatic solid tumors, and that expression of an appropriate transgene at tumor loci might mediate cures of metastatic disease. To test this hypothesis, we injected HB1.F3.C1 cells transduced to express an enzyme that efficiently activates the anti-cancer prodrug CPT-11 intravenously into mice bearing disseminated neuroblastoma tumors. The HB1.F3.C1 cells migrated selectively to tumor sites regardless of the size or anatomical location of the tumors. Mice were then treated systemically with CPT-11, and the efficacy of treatment was monitored. Mice treated with the combination of HB1.F3.C1 cells expressing the CPT-11-activating enzyme and this prodrug produced tumor-free survival of 100% of the mice for >6 months (P<0.001 compared to control groups).
  
  
  CONCLUSIONS
  The novel and significant finding of this study is that it may be possible to exploit the tumor-tropic property of stem or progenitor cells to mediate effective, tumor-selective therapy for metastatic tumors, for which no tolerated curative treatments are currently available.
authors.affiliation: Divisions of Hematology/Hematopoietic Cell Transplantation and Neurosciences, and Department of Professional Education, City of Hope National Medical Center, Duarte, California, United States of America. kaboody@coh.org
authors.forename: Karen S
authors.initials: KS
authors.lastname: Aboody
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Bush
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garcia
authors.forename: Marianne Z
authors.initials: MZ
authors.lastname: Metz
authors.forename: Joseph
authors.initials: J
authors.lastname: Najbauer
authors.forename: Kristine A
authors.initials: KA
authors.lastname: Justus
authors.forename: Doris A
authors.initials: DA
authors.lastname: Phelps
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Remack
authors.forename: Karina Jin
authors.initials: KJ
authors.lastname: Yoon
authors.forename: Shanna
authors.initials: S
authors.lastname: Gillespie
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Carlotta A
authors.initials: CA
authors.lastname: Glackin
authors.forename: Philip M
authors.initials: PM
authors.lastname: Potter
authors.forename: Mary K
authors.initials: MK
authors.lastname: Danks
mesh_terms: D000818:Animals; D001483:Base Sequence; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000637:transplantation; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000201:enzymology / Q000637:transplantation; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology / Q000556:secondary / Q000628:therapy; D011355:Prodrugs / Q000493:pharmacokinetics / Q000627:therapeutic use; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous
chemical_list: D017931:DNA Primers; D011355:Prodrugs; D011994:Recombinant Proteins; D000077146:Irinotecan; C072888:CPT-11 converting enzyme; D002265:Carboxylic Ester Hydrolases; D002166:Camptothecin