CYTOTOXIC-CELL FUNCTION AND PHENOTYPIC ANALYSIS OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS IN CANCER-PATIENTS TREATED WITH LOW-DOSE INTERLEUKIN-2 AND MITOMYCIN-C

We previously found that the ability of peripheral blood mononuclear c ells (PBM) of cancer patients to generate lymphokine-activated killer (LAK) cells became remarkably augmented after mitomycin C administrati on. On the basis of the clinical findings, we designed a treatment reg imen comprised of 12 mg/M2 mitomycin C i.v. on day 1 and 700 U/m2 reco mbinant interleukin-2 (IL-2) i. v. every 12 h from day 4 through day 8 . Of 25 patients with advanced carcinoma, 9 had a partial response and 3 had a minor response. Cytotoxic cell function, including natural ki ller activity, lymphokine-activated killer (LAK) activity, and the abi lity to generate LAK cells, and lymphocyte subsets in PBM was measured 1 day before and after either the first or second course of this ther apy. The relationship between these parameters and the clinical antitu mor response to this treatment was examined. Although the cytotoxic ac tivities were significantly augmented after either the first or second treatment course, no positive correlation was observed between the ch anges in these cytotoxic activities and the clinical response to this therapy, when patients who either showed a partial response or whose d isease remission was partial or minor were defined as responders. Furt her, phenotypic analysis showed a significant increase in CD2+, CD3+, CD4+ and CD4+Leu8- cells after the first course, and CD25+ cells after either the first or second course of this treatment. The percentages of CD2+ and CD25+ cells were significantly elevated only in responders but not in nonresponders, suggesting the increase in these subsets wa s related to clinical response.