E1B-deleted adenovirus (dl1520) gene therapy for patients with primary andsecondary liver tumors

Clinical studies were performed with a recombinant mutant adenovirus with a n E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patie nts with irresectable primary and secondary liver tumors. A phase I study s howed that dl1520 was well tolerated when administered directly intratumora lly, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU, Ultr astructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cel l death after virus infection: a preapoptotic sequence and necrosis, A phas e TI study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvem ent in the recombinant vector design will be needed in order to achieve bet ter clinical response.