INGN-241: Cancer gene therapy

The profound toxic effects of conventional cancer therapies such as chemo- and radiotherapy and the nonspecific side effects of small-molecule inhibitors of signaling proteins mandate more effective and preferably nontoxic approaches for treating cancer. An ideal cancer therapeutic should specifically and selectively target not only neoplastic cells but also a tumor's blood supply, and should effectively eradicate both primary and metastatic tumors with equal efficiency. Although this combination of properties in a single or even multiple agents seems untenable, melanoma differentiationassociated gene 7/interleukin-24 (MDA-7/IL24) exhibits all of these traits, thus attaining the unique status of a potential 'magic bullet' for cancer. This unique IL-10 family member cytokine induces apoptosis only in cancer cells without harming normal cells, inhibits tumor angiogenesis, stimulates an antitumor immune response, synergizes with radiation, chemotherapy, small molecules and monoclonal antibodies, and thereby inhibits both primary and metastatic tumors by eliciting a profound 'bystander' antitumor effect. A phase I clinical trial has been successfully completed using a replication-incompetent adenovirus expressing MDA-7/1124 (INGN-241), demonstrating safety, lack of toxicity and significant objective clinical responses. Thus, MDA-7/IL24 therapy might promote the elimination of primary and distant tumors, resulting in prolonged survival of patients and establishing a 'cure'.