ADVANCES IN ADENOVIRAL VECTORS FOR CANCER GENE-THERAPY

Delineation of the molecular basis of cancer affords the possibility o f specific intervention at the molecular level for therapeutic purpose s. To this end, viral and non-viral vectors have been designed for del ivery 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 b een particularly efficient for in vivo gene transfer. Importantly, num erous 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 adenov iruses can become an effective and common place strategy for cancer tr eatment. An overriding obstacle is the basic ability to deliver therap eutic genes quantitatively, and specifically, into tumour cells. In ad dition, transgene expression in transduced target cells has not been p rolonged enough for certain applications. The short-term expression is due both to the adenoviral non-integrative life cycle and to potent i nflammatory and immunological responses against the vector and transge ne. Here we review a number of diverse advances in the design of adeno viral vectors for overcoming these obstacles. As vector technology ful fils these requirements for obtaining the 'targetable-injectable' vect or, it is anticipated that promising results already observed in precl inical studies will translate quickly into the clinic.