Interferon alpha 2b gene delivery using adenoviral vector causes inhibition of tumor growth in xenograft models from a variety of cancers

A recombinant adenovirus expressing human interferon alpha 2b driven by the cytomegalovirus promoter, IACB, was shown to produce and secrete biologica lly active protein in vitro and in vivo. Intravenous administration of IACB in Buffalo rats resulted in circulating levels of biologically active huma n interferon at 70,000 international units/mL for up to 15 days. Distributi on of interferon protein after IACB administration was different from that seen with the subcutaneous delivery of interferon protein. Higher levels of interferon protein were observed in liver and spleen after IACB delivery c ompared to protein delivery. The antitumor efficacy of IACB, as measured by suppression of tumor growth, was tested in athymic nude mice bearing estab lished human tumor xenografts from different types of human cancer. Subcuta neous tumors most responsive to the intratumoral administration of IACB ran ked as U87MG (glioblastoma) and K562 (chronic myelogenous leukemia), follow ed by Hep 3B (hepatocellular carcinoma) and LN229 cells (glioblastoma). Int ravenous administration of IACB in animals bearing U87MG or Hep 3B xenograf ts was also effective in Suppressing tumor growth, although to a lesser ext ent than the intratumoral administration. IACB was also tested in a metasta tic model in beige/SCID mice generated with H69 (small cell lung carcinoma) cells and was found to prolong survival in tumor-bearing animals. This sug gested that interferon gene delivery can be effective in suppressing tumor growth in a wide variety of cells.