Adenoviral Gene Expression and Replication in Human Tumor Explant Models

Promising results have been reported from numerous studies with replication-selective oncolytic adenoviral mutants as novel treatments for a variety of cancers. Most of these studies were performed in cancer cell lines, dissociated tumor tissue, or animal models, and the predictive utility for efficacy and safety in the clinical setting is unclear. Indeed, the outcome of many clinical trials with viral mutants that demonstrated high efficacy preclinically has so far been disappointing, necessitating better test models. To this end, we developed a methodology using primary human cancer specimens for evaluation of cytotoxicity ex vivo including colorectal liver metastasis, ovarian, breast, colon, and prostate carcinomas. Under optimized culture conditions, primary human tumor tissue remained viable for up to 48 h, enabling evaluation of viral mutants in tissue with intact morphology. This assay may have great utility to investigate novel viral mutants and to identify treatment sensitive cancers by assessing specific oncolytic mutants in individual cases.