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  • Title: Evaluation of adenovirus vectors containing serotype 35 fibers for tumor targeting.
    Author: Ni S, Gaggar A, Di Paolo N, Li ZY, Liu Y, Strauss R, Sova P, Morihara J, Feng Q, Kiviat N, Touré P, Sow PS, Lieber A.
    Journal: Cancer Gene Ther; 2006 Dec; 13(12):1072-81. PubMed ID: 16874361.
    Abstract:
    There is growing evidence from in vitro studies that subgroup B adenoviruses (Ad) can overcome the limitations in safety and tumor transduction efficiency seen with commonly used subgroup C serotype 5-based vectors. In this study, we confirm that the expression level of the B-group Ad receptor, CD46, correlates with the grade of malignancy of cervical cancer in situ. We also demonstrate the in vivo properties of Ad5-based vectors that contain the B-group Ad serotype 35 fiber (Ad5/35) in transgenic mice that express CD46 in a pattern and at a level similar to humans. Upon intravenous and intraperitoneal injection, an Ad5/35 vector did not efficiently transduce normal tissue, but was able to target metastatic or intraperitoneal tumors that express CD46 at levels comparable to human tumors. When an oncolytic Ad5/35-based vector was employed, in both tumor models antitumor effects were observed. Furthermore, injection of Ad5/35 vectors into CD46 transgenic mice caused less innate toxicity than Ad5 vectors. Our data demonstrate that Ad vectors that target CD46 offer advantages over Ad5-based vectors for treatment of cancer.
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