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


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Akbulut H., Tang Y., Akbulut K. G. , Maynard J., Deisseroth A.

GENE THERAPY, cilt.17, sa.11, ss.1333-1340, 2010 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 17 Konu: 11
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1038/gt.2010.93
  • Dergi Adı: GENE THERAPY
  • Sayfa Sayıları: ss.1333-1340

Özet

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 hMUC1/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. Gene Therapy (2010) 17, 1333-1340; doi:10.1038/gt.2010.93; published online 1 July 2010