INTRALESIONAL TREATMENT OF ESTABLISHED MURINE PRIMARY RENAL TUMOR WITH INTERLEUKIN-4 - LOCALIZED EFFECT ON PRIMARY TUMOR WITH NO IMPACT ON METASTASES

In an effort to develop new strategies for immunotherapy of metastatic renal cell carcinoma, we investigated the therapeutic potential of in terleukin-4 in a visceral renal tumor using the murine Renca renal ade nocarcinoma model. Renca cells were implanted underneath the renal cap sule of Balb/c mice to induce a primary tumor that spontaneously metas tasized to several organs. Established primary renal tumors 4 to 6 mm. in diameter were treated by intralesional administration of recombina nt murine interleukin-4 (IL-4). This treatment caused a marked inhibit ion of the primary tumor growth but had little effect on the progressi on of metastases in the liver, mesentery and lungs. Immunohistochemist ry studies performed on renal tumor sections showed a macrophage infil tration that became predominant 7 days after IL-4 treatment. CD8+ T ce lls were also observed at the periphery and within the tumor. These da ta suggest that IL-4 mediated a potent antitumor effect when administe red intralesionally although its effects remained localized with no im pact on metastases at distant sites. Interleukin-4 antitumor activity seems to be mediated by recruitment of macrophages and T cells in the tumor.