| Abstract: |
Natural killer (NK) cells are believed to contribute to the clinical efficacy of cancer immunotherapy using recombinant interleukin-2 (rIL-2) in humans. In previous trials of high-dose i.v. rIL-2, however, no correlation has been established between circulating NK cells and treatment response. Between January 1989 and October 1990, we treated a total of 47 outpatients with advanced tumors using low-dose s.c. rIL-2 and interferon-α-2 (rIFN-a). Therapy consisted of a 2-day rIL-2 pulse at 18 million IU/m2/ day, followed by 6 weeks of rIL-2 (3.6 x 106-4.8 x 106 IU/m2/day x 5 days/week) and rIFN-α (5 x 106-6 x 106U/m2 x 3/week). Before and after therapy, we phcnotypically evaluated circulating lymphocytes and correlated them with clinical response. During 6-week therapy, peripheral blood lymphocytes bearing the CD56 (NK-cell-associated) surface antigen were increased significantly (p < 0.005) in treatment responders [complete response (CR) and partial response (PR), n = 10; 3.8-fold] and stable disease (SD) patients (n = 20; 2.1-fold), while patients with progressive disease (PD, n = 17) exhibited no significant expansion of circulating NK cells (p > 0.1). After one 6-week treatment cycle, CR/PR patients had significantly more peripheral NK cells, when compared with patients in SD (1.6-fold) and PD (1.9-fold) (p < 0.04). The overall number of circulating lymphocytes was also increased upon therapy (1.6-fold; p < 0.001). but remained independent of response (p > 0.4). These data demonstrate that s.c. rIL-2 and s.c. rIFN-α produce a significant increase in peripheral blood NK cells; this expansion correlates significantly with treatment response in advanced tumor patients receiving long-term combination immunotherapy at outpatient doses. © 1993 S. Karger AG, Basel. |
| Keywords: |
clinical article; controlled study; treatment outcome; advanced cancer; neoplasms; cancer immunotherapy; melanoma; drug administration schedule; kidney neoplasms; hodgkin disease; colorectal neoplasms; lymphoma, b-cell; carcinoma, renal cell; recombinant proteins; natural killer cell; killer cells, natural; blood cell; immunophenotyping; t-lymphocyte subsets; antigens, cd; kidney cancer; injections, subcutaneous; interleukin-2; recombinant interleukin 2; interferon-α; natural killer cells; interferon alfa-2b; subcutaneous drug administration; human; priority journal; article; outpatient immunotherapy; recombinant alpha2 interferon
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