Advances in adenoviral vectors for cancer gene therapy

Delineation of the molecular basis of cancer affords the possibility of specific intervention at the molecular level for therapeutic purposes. To this end, viral and non-viral vectors have been designed for delivery and expression of genes into target malignant and non-malignant cells. Gene transfer by available vectors, applied in both the ex vivo and in vivo contexts, has resulted frequently in the desired cellular phenotypical changes. In this regard, recombinant adenoviruses have been particularly efficient for in vivo gene transfer. Importantly, numerous human clinical protocols using adenoviruses have rapidly entered into Phase I clinical trials. However, major vector-related problems remain to be solved before the transfer of therapeutic genes by adenoviruses can become an effective and common place strategy for cancer treatment. An overriding obstacle is the basic ability to deliver therapeutic genes quantitatively, and specifically, into tumour cells. In addition, transgene expression in transduced target cells has not been prolonged enough for certain applications. The short-term expression is due both to the adenoviral non-integrative life cycle and to potent inflammatory and immunological responses against the vector and transgene. Here we review a number of diverse advances in the design of adenoviral vectors for overcoming these obstacles. As vector technology fulfils these requirements for obtaining the 'targetable-injectable' vector, it is anticipated that promising results already observed in preclinical studies will translate quickly into the clinic.