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 biopsie s of patients with superficial bladder cancer before and after intrave sical human recombinant interleukin-2 (rhuIL-2) therapy (three cases a t I MIU, four cases at 18 MIU and two cases at 54 MIU), was investigat ed. There was a slight but significant increase in the total number of circulating leucocytes, harvested from blood using density gradient t echnique, after intravesical rhuIL-2 treatment. Thus the mean +/- SD o f seven cases before and after (more than 30 days of) IL-2 were 1.24 /- 0.32 x 10(9)/1 and 1.50 +/- 0.46 x 10(9)/1 respectively (t-test, P = 0.032). However, this was substantially less than in samples collect ed after subcutaneously (six cases) and intravenously (seven cases) ad ministering rhuIL-2, the results of which were 1.09 +/- 0.46 x 10(9)/1 versus 2.22 +/- 0.68 x 10(9)/1 (P = 0.016) and 0.84 x 10(9)/1 Versus 2.3 x 10(9)/1 (P = 0.004) respectively. There was no demonstrable alte ration 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 positivi ty 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 n ine cases before treatment. Given the lack of the expected major immun ological 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 a nd alternative schedules based on those developed from systemic treatm ent need exploration.