Generation of an adenovirus vector for gene therapy of pituitary tumor

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Adenovirus vectors (Ads) have been employed for a wide variety of cancer gene therapy applications to date. This utility has derived principally from the unparalleled ability of these agents to accomplish efficient gene delivery to tumor targets. Unfortunately, translation of these advantages has been more difficult to accomplish in human clinical gene therapy trials for cancer. Critical problems to overcome are low efficiency and lack of selectivity of currently available gene transfer systems. Adaptation of Ad for cancer gene therapy applications would thus ideally embody these two mandates-the ability to accomplish adenovirus receptor (CAR)-independent gene delivery as a means to improve vector efficiency for tumor targets and the ability to avoid liver sequestration as a means to limit potential vector related toxicity. Herein, we compared gene transfer efficiencies of Ad serotype 5 (Ad5) capsid-based 'longer-shafted' Ad vector with a somatostatin ligand (SS-14) in the HI-loop of the fiber knob (Ad5longSS-14VEGF) to wild-type Ad vector in vitro. Ad5longSS-14VEGF significantly reduced infectivity in CAR-positive cells (normal organ model). On the other hand, Ad5longSS-14VEGF significantly increased infectivity in SS-14 receptor-positive cells (pituitary tumor model) compared with Ad5. We suggest that Ad vectors with artificial fiber shaft extension in combination with a somatostatin ligand in the HI-loop of the fiber knob may be useful for gene therapy of pituitary tumor.