ANTISENSE APPROACHES TO CANCER GENE-THERAPY

Recent advances in the use of oligodeoxynucleotide and plasmid-derived RNA as antisense agents of special relevance to cancer gene therapy are summarized with emphasis on agents and systems which have lead to clinical trials and/or regression of established tumors in animal model systems. Transformed cell lines bearing plasmids and viruses designed for the transcription of antisense RNA have the advantage that they can be characterized thoroughly and the effects of antisense RNA on target gene expression and phenotype can be studied easily in vivo. Promising results make the considerable efforts of applying oligodeoxynucleotides in whole animals and in clinical trials more plausible. Conversely, oligodeoxynucleotide experiments which yield promising results in tissue culture can be generalized to the in vivo setting by development of clones of cells bearing plasmid-derived antisense RNA against the same target. Several examples of the concordant results for oligodeoxynucleotide and plasmid-derived antisense RNA against the same target are considered. The importance of examination of antisense effects in syngeneic and immunocompetent hosts is illustrated by studies of insulin-like growth factor and insulin-like growth factor receptor where tumor regression and protection against, tumor formation have been observed for particular cell types in defined settings.