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Adoptive Immunotherapy of Human Cancer: The Cytokine Cascade and Monocyte Activation following High-Dose Interleukin 2 Bolus Treatment¹

Department of Hematology and Oncology, Istituto Superiore di Sanità [G. B., R. M., G. G., E. M., U. T., C. P.]; Blood Transfusion Center [G. I.] and Instituto di Patologia Medica (VI) [G. M.]; University "La Sapienza" and Division of Medical Oncology I, Istituto Regina Elena [E. M. R., P. C., F. C.], Rome, Italy

Serum concentration kinetics of -interferon (IFN-), neopterin, 2'-5'A synthetase and tumor necrosis factor were determined in five cancer patients undergoing adoptive immunotherapy with high-dose interleukin 2 (IL-2) bolus infusion and lymphokine-activated killer cells according to the National Cancer Institute, NIH protocol.

In all cases a significant increase of these markers was observed after IL-2 treatment. This suggests that the antitumor effect of high-dose IL-2 bolus administration may be in part mediated by activation of a cascade of endogenous cytokines including IFN- and tumor necrosis factor .

After IL-2 bolus injection, the kinetics of neopterin was similar but delayed when compared to that of IFN-: this suggests that macrophages, the specific source of neopterin, become activated by IFN- following IL-2-mediated lymphocyte induction, thus implying a possible role for macrophages in the antitumor effects mediated by IL-2 and lymphokineactivated killer cells.

¹ This study was supported by a grant from Istituto Superiore di Sanità, Rome, Italy ("Italy-USA Project on Therapy of Tumors").

² To either of whom requests for reprints should be addressed, at Department of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.

Received 1/ 2/90. Accepted 6/ 4/90.

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