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Regional administration of natural killer cells in a rat hepatic metastasis model results in better tumor infiltration and anti‐tumor response than systemic administration

A syngeneic rat liver metastasis model, the CC531 colon carcinoma cell line in Wag rats, was used to study the homing properties and anti‐tumor effects of adoptively transferred, interleukin‐2 (IL‐2)‐activated, cultured natural killer (A‐NK) cells. To identify the route of administration that gives the highest tumor infiltration, 1.5 × 108 A‐NK cells were dyed with fluorescent rhodamine and injected via 4 different routes into rats, bearing subcapsularly induced (day 10) liver metastases. The routes chosen were: jugular vein, portal vein, hepatic artery and directly into the peritoneal cavity (i.p). The rats were sacrificed 20 hr after administration of A‐NK cells. The highest (p < 0.05) infiltration of tumors by A‐NK cells was found both at the tumor border and in the tumor center after injection via the hepatic artery: 65 ± 7 A‐NK cells/mm2 at the tumor border and 26 ± 14 A‐NK cells/mm2 in the center of the tumor (jugular vein infusion: 32 ± 10 and 9 ± 5 A‐NK cells/mm2, respectively; portal vein infusion: 36 ± 13 and 7 ± 4 A‐NK cells/mm2, respectively). No A‐NK cells were detected in the liver after i.p. injection. Rats bearing day 5 tumors were injected with 1.5 × 108 A‐NK cells via the hepatic artery or via the jugular vein (n = 5 and n = 6 respectively). Regional administration of A‐NK cells via the hepatic artery resulted in a significant (p < 0.05) lower weight (35 ± 23 mg) of tumors than did systemic administration (70 ± 10 mg). Our results suggest that both the level of tumor infiltration by adoptively transferred A‐NK cells and the therapeutic outcome depend on the route of administration. Int. J. Cancer 75:233–238, 1998. © 1998 Wiley‐Liss, Inc.