title: Addition of adenoviral vector targeting of chemotherapy to the MUC-1/ecdCD40L VPPP vector prime protein boost vaccine prolongs survival of mice carrying growing subcutaneous deposits of Lewis lung cancer cells.
abstract: We studied the effect of adding chemotherapy or vector targeted chemotherapy to the administration of an Ad-sig-hMUC-1/ecdCD40L adenoviral vector prime-hMUC-1/ecdCD40L protein boost cancer vaccine (designated hMUC-1/ecdCD40L VPPP vaccine), which were administered to test mice 10 days following subcutaneous (s.c.) inoculation of 500,000 Lewis Lung Carcinoma cells, at a time when the average volume of the s.c. tumors was 50 cu mm. The survival of hMUC-1/ecdCD40L VPPP vaccine-treated mice was twice as long as untreated mice. Addition of vector-targeted chemotherapy (AdCMVCDIRESE1A/5FC) to the hMUC-1/ecdCD40L VPPP vaccine 10 days after tumor inoculation significantly (P=0.0062) prolonged the survival of the test mice over administration of the hMUC-1/ecdCD40L VPPP vaccine alone or the control mice (P<0.00001). Interestingly, the combination of the AdCMVCDIRESE1A/5FC vector-targeted chemotherapy to the hMUC-1/ecdCD40L VPPP vaccine decreased the levels of CD44(+)CD24⁻ cells in s.c. deposits of the human MUC-1-positive Lewis Lung Cancer cell line (LL2/LL1hMUC-1) by 20 fold. These results suggest that the addition of vector-targeted chemotherapy to an adenoviral-based cancer vaccine is a strategy that deserves further testing.
authors.affiliation: Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Akbulut
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: K G
authors.initials: KG
authors.lastname: Akbulut
authors.forename: J
authors.initials: J
authors.lastname: Maynard
authors.forename: A
authors.initials: A
authors.lastname: Deisseroth
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D023201:CD40 Ligand / Q000235:genetics*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; C060192:MUC1 protein, human; D018396:Mucin-1; D023201:CD40 Ligand