Clinical and immunological effect of intravesical interleukin-2 on superficial bladder cancer

Using immunocytochemical techniques the pattern of T cell markers and MHC antigens on peripheral blood mononuclear cells, and tumour biopsies of patients with superficial bladder cancer before and after intravesical human recombinant interleukin-2 (rhuIL-2) therapy (three cases at 1 MIU, four cases at 18 MIU and two cases at 54 MIU), was investigated. There was a slight but significant increase in the total number of circulating leucocytes, harvested from blood using density gradient technique, after intravesical rhuIL-2 treatment. Thus the mean +/- SD of seven cases before and after (more than 30 days of) IL-2 were 1.24 +/- 0.32 x 10(9)/l and 1.50 +/- 0.46 x 10(9)/l respectively (t-test, P = 0.032). However, this was substantially less than in samples collected after subcutaneously (six cases) and intravenously (seven cases) administering rhuIL-2, the results of which were 1.09 +/- 0.46 x 10(9)/l versus 2.22 +/- 0.68 x 10(9)/l (P = 0.016) and 0.84 x 10(9)/l versus 2.3 x 10(9)/l (P = 0.004) respectively. There was no demonstrable alteration in the percentage of cells positive for CD3, CD4, CD8, CD25 or CD56 in peripheral blood or urine populations in six patients treated with intravesical IL-2, or the pattern of MHC class I or II expression on tumour biopsies before and after treatment. Though this could have been a reflection of the fact that most of the cases had normal class I expression, there was one tumour with complete loss and one tumour with very low expression among the three cases showing stroma positivity for HLA-A3 antigens. Neither of these was altered by IL-2 treatment, nor was class II antigen expression, which was positive in five of nine cases before treatment. Given the lack of the expected major immunological changes and the poor clinical responses (one of nine complete responses lasted 3 months), it is concluded that the schedule has not produced an adequate dose intensity to induce lymphocyte activation and alternative schedules based on those developed from systemic treatment need exploration.