REGIONAL ADMINISTRATION OF NATURAL-KILLER-CELLS IN A RAT HEPATIC METASTASIS MODEL RESULTS IN BETTER TUMOR INFILTRATION AND ANTITUMOR 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-tu mor effects of adoptively transferred, interleukin-2 (IL-2)-activated, cultured natural killer (A-NK) cells. To identify the route of admini stration that gives the highest tumor infiltration, 1.5 x 10(8) A-NK c ells were dyed with fluorescent rhodamine and injected via 4 different routes into rats, bearing subcapsularly induced (day 10) liver metast ases. The routes chosen were: jugular vein, portal vein, hepatic arter y and directly into the peritoneal cavity (i.p.) The rats were sacrifi ced 20 hr after administration of A-NK cells. The highest (p < 0.05) i nfiltration 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/mm(2) at the tumor border and 26 +/- 14 A-NK cells/mm(2 ) in the center of the tumor (jugular vein infusion: 32 +/- 10 and 9 /- 5 A-NK cells/mm(2), respectively; portal vein infusion: 36 +/- 13 a nd 7 +/- 4 A-NK cells/mm(2), respectively). No A-NK cells were detecte d in the liver after i.p. injection. Rats bearing day 5 tumors were in jected with 1.5 x 10(8) A-NK cells via the hepatic artery or via the j ugular 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 administrati on (70 +/- 10 mg). Our results suggest that both the level of tumor in filtration by adoptively transferred A-NK cells and the therapeutic ou tcome depend on the route of administration. (C) 1998 Wiley-Liss, Inc.