Inhibition of tumor growth by the intralesional administration of interleukin-3 into mice implanted with solid tumors

The anitumor activity of three interleukin-3 (IL-3) preparations administered intralesionally into mice bearing syngeneic solid tumors was investigated. IL-3 preparations used in this study included S-IL-3, which was isolated from the culture fluid of murine inguinal lymph node cells stimulated with an arabinomannan extracted from Mycobacterium tuberculosis (SSM), the culture fluid of WEHI-3 cells (W-IL-3) and recombinant IL-3 (rIL-3). When a 1,500 U/kg dose of S-IL-3 or W-IL-3 was injected intralesionally into BALB/c mice bearing Meth-A solid tumors three time per week beginning 3 days after tumor inoculation, tumor growth was inhibited by 60% or 74% at 24 days after tumor inoculation, respectively. In these experiments, 1 unit of IL-3 activity was determined to be the concentration that induced 50% of maximal proliferation of an IL-3 dependent cell line (FCD-P₂ cells). The administration of this dose of rIL-3 inhibited tumorgrowth by 34%. When these three preparations of IL-3 were pretreated with anti-lL-3 monoclonal antibody in vitro, the antitumor activity, as well as their growth promoting activity on FDC-P₂ cells, was eliminated. Since direct cytotoxic activities of these IL-3 preparations against cultured Meth-A tumor cells in vitro have not been demonstrated, these results suggest that their antitumor activities might be expressed through interactions between tumor cells and antitumor effector cells which were stimulated by the intralesional administration of the IL-3 preparations.