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Biomedicines 2014, 2(1), 110-131; doi:10.3390/biomedicines2010110

Feasibility of Applying Helper-Dependent Adenoviral Vectors for Cancer Immunotherapy

Department of Medicine, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
* Author to whom correspondence should be addressed.
Received: 20 December 2013 / Revised: 25 February 2014 / Accepted: 26 February 2014 / Published: 10 March 2014
(This article belongs to the Special Issue Gene Therapy Used in Cancer Treatment)
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Adenoviruses (Ads) infect a broad range of tissue types, and derived vectors have been extensively used for gene therapy. Helper-dependent Ad vectors (HDAds), devoid of viral coding sequences, allow for insertion of large or multiple transgenes in a single vector and have been preclinically used for the study of genetic disorders. However, the clinical application of Ad vectors including HDAds for genetic disorders has been hampered by an acute toxic response. This characteristic, while disadvantageous for gene replacement therapy, could be strategically advantageous for the activation of an immune response if HDAds were used as an adjunct treatment in cancer. Cancer treatments including immunotherapy are frequently limited by the inhibitory environment produced by both tumors and their stroma, each of which express numerous inhibitory molecules. Hence, multiple inhibitory mechanisms must be overcome for development of anti-tumor immunity. The large coding capacity of HDAds can accommodate multiple immune modulating transgenes that could produce a combined effect to overcome tumor-derived inhibition and ensure intratumoral effector T-cell proliferation and function. In this review, we discuss the potential advantages of HDAds to cancer immunotherapy based on potent host immune responses to Ads.
Keywords: Helper-dependent adenoviral vector; immune response; pattern-recognition receptor; cancer immunotherapy Helper-dependent adenoviral vector; immune response; pattern-recognition receptor; cancer immunotherapy
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Farzad, L.M.; Suzuki, M. Feasibility of Applying Helper-Dependent Adenoviral Vectors for Cancer Immunotherapy. Biomedicines 2014, 2, 110-131.

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