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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

Gene Therapy volume 17, pages 1333–1340 (2010)Cite this article

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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.

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Acknowledgements

We acknowledge support from the support of the SKCC by Sidney Kimmel and the following grants to Albert Deisseroth: DOD (Grants 17999457 and BC022063), the California Breast Cancer Research Program (CBCRP 12IB-0159), the NIH Grant PPG (CA 104898), a grant from the Kaye and Richard Woltman Foundation, and a grant from the Breast Cancer Research Foundation. We acknowledge support to Hakan Akbulut from the Turkish Academy of Sciences (TUBA-GEBIP-2001-1), the National Cancer Institute of United States of America, The Lechner/Haag Foundation and UICC-Yamagiwa-Yoshida international study grants. The views expressed are the result of independent work and do not represent the views or findings of the US FDA or the US government.

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Authors and Affiliations

  1. Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey

    H Akbulut

  2. Department of Genetic Therapy, Sidney Kimmel Cancer Center, San Diego, CA, USA

    Y Tang, J Maynard & A Deisseroth

  3. Department of Physiology, Gazi University School of Medicine, Ankara, Turkey

    K G Akbulut

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Correspondence to A Deisseroth.

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Akbulut, H., Tang, Y., Akbulut, K. et al. 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. Gene Ther 17, 1333–1340 (2010). https://doi.org/10.1038/gt.2010.93

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