J.Jpn. Surg. Soc.. 88(7): 802-807, 1987

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Original article

INJECTION OF INTERLEUKIN-2 (IL-2) INTO THE TUMOR-BEARER’S SPLEEN AUGMENTS　LYMPHOKINE-ACTIVATED KILLER (LAK) ACTIVITY IN VITRO AND INHIBITS TUMOR METASTASIS

The effect of interleukin-2 (IL-2), injected directly into the tumor-bearer’s spleen, on inhibition of tumor metastasis was evaluated. C3H/HeN mice were inoculated intradermally with 2×10⁶ X5563 syngeneic tumor cells on day 0, and the tumor was surgically resected on day 10. The operation failed to prevent tumor death of these mice within 3 weeks. Autopsy of these mice revealed that death was due to systemic metastasis of tumor cells to lymphoid organs including the liver although the tumors had been successfully removed without any visible local recurrence. In this model, we administered IL-2 by intrasplenic injection daily for 3 days after operation. Mice treated with an intrasplenic injection of IL-2 showed a significantly prolonged survival time. Histological findings after this treatment revealed lymphoid cell proliferation of the spleen, no metastatic foci were found in the liver. Lymphokine-activated killer (LAK) activity from IL-2 injected spleen was also augmented. Intravenous (i.v.) and subcutaneous (s.c.) administration of IL-2 were not effective. A major difficilty in achieving significant immunologic effect in vivo by IL-2 infusion is the relatively short half-life of IL-2. Therefore IL-2 administered directly into the responding lymphoid organ is theoretically reasonable. In fact, treatment with intrasplenic injection of IL-2 significantly augmented the antitumor activity. Splenic arterial infusion of IL-2 may be an appropriate route of administration for adjuvant immunotherapy in human cancer.

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