THE SYNERGISTIC ANTITUMOR EFFECT OF RECOMBINANT INTERLEUKIN-1 AND LOW-DOSE OF CYCLOPHOSPHAMIDE IN TUMOR-BEARING MICE

Intraperitoneal (i.p.) treatment of MOPC104E ascitic tumor-bearing BALB/c mice with interleukin-1 (IL-1) followed by a low dose of cyclophosphamide ( CPA) resulted in synergistic prolongation of their survival time. This antitumor effect was abolished when administration of CPA preceded that of IL-1. The combined i. p. therapy also eradicated subcutaneous ( s.c.) tumors, indicating a systemically operating antitumor mechanism. In Winn assay, splenocytes from MOPC104E-bearing mice treated with the combined therapy completely suppressed the growth of MOPC104E cells, but not that of another syngeneic tumor cell line, RL female -8 cells. This tumor-neutralizing activity was completely abrogated by treatment with anti-asialo-GM1 or anti-Thy1.2 and complement, and reduced by treatment with anti-Lyt2.2 and complement. Treatment of splenocytes with 1-leucine methyl ester (Leu0Me), which depletes natural killer (NK) cells and macrophages in vitro, did not affect the neutralizing activity. (C) 1994 Wiley-Liss, Inc.