Immunotherapy III: Combinatorial molecular immunotherapy - A synthesis and suggestions

Animal models have clearly shown that tumor cells may be amenable to molecular manipulation which can result in immune activation and rejection of unmodified cells. The challenge now is to design clinical trials which have a realistic chance of success, (although the definition of 'success' is itself an important issue). How should such a strategy be formulated? A review of the previous fifteen years since the first (immune) gene transfer studies were reported, encompasses a great wealth of data. Unfortunately, far from crystallising a set of unifying principles, these diverse reports shroud us in a fog of uncertainty as to how best to proceed. However, if this technology is to have practical, widespread application in the treatment of cancer patients, it is necessary to identify certain critical immunological goals which any protocols should achieve. Clear elucidation of these goals, by unifying the huge amount of disparate experimental data, must eventually be accomplished. In this chapter, we have reviewed the literature covering the era of molecular immunotherapy. We propose four general goals around which widely applicable clinical protocols, not necessarily dependent upon tumour type or experimental bias, might be based and suggest how they may be achieved in the context of gene transfer.