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 x 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 x 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.