The therapeutic activity in cancer of IL-2 in combination with other cytokines

Animal studies have been carried out to assess the antitumour efficacy of recombinant interleukin-2 (rIL-2) in combination with other cytokines. In several murine tumour models, rIL-2 in combination with recombinant alpha interferon (rIFN-alpha) elicits a potent antitumour response which is often greater than that which can be reached with the individual agents at non-toxic doses. By contrast, recombinant gamma interferon (rIFN-gamma) usually fails to potentiate the antitumour response to rIL-2. Recombinant alpha tumour necrosis factor (rTNF) can synergize with rIL-2 in some circumstances, but, as with the rIL-2/rIFN-alpha combination, the correct regimen is critical for generating a potent response without overt toxicity. Although appropriate cytokine combinations can lead to markedly enhanced tumour infiltration by lymphocytes, it is not clear that only a single type of lymphocyte is invariably involved in the antitumour response or, for that matter, the toxic side effects; nor has the mechanism of action of any of the cytokines in the therapeutic action been unequivocally elucidated. Finally, results of early clinical studies appear to be consistent with results in preclinical models: promising clinical responses to the combination of rIL-2 and rIFN-alpha have already been observed and further study is merited.