TNFalpha gene delivery therapy for solid tumors

Multimodality therapy, including adjuvant and neoadjuvant chemotherapy and radiotherapy, is now the mainstay of treatment for the majority of non-hematologic cancers. Host toxicity can, however, be significant, which may contribute to local and/or systemic failures. Novel adjunctive treatments that can limit systemic exposure while synergizing with standard therapy hold promise in the fight against an increasing number of cancers.

We discuss a TNFalpha gene delivery system used to generate high levels of intratumoral TNFalpha, while limiting systemic exposure. The delivery system utilizes a replication-deficient adenoviral vector. When injected intratumorally and activated by external beam radiation, infected cells synthesize and locally secrete large amounts of TNFalpha.

This review will provide the reader with a thorough understanding of the gene-based TNFalpha delivery system with special emphasis on product characteristics, mechanisms of action, clinical efficacy, safety and tolerability.

The TNFalpha gene delivery system holds promise as an adjunctive agent for improved local control and increasing resectability rates for many solid tumors. The completion of several ongoing randomized trials will help to better define the role for TNFalpha gene delivery therapy in the treatment of solid tumors.