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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
Author(s) -
Hagenaars Martin,
Ensink N. Geeske,
Koelemij Ron,
Basse Per H.,
Eggermont Alexander M. M.,
van de Velde Cornelis J. H.,
Fleuren Gert Jan,
Kuppen Peter J. K.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980119)75:2<233::aid-ijc11>3.0.co;2-e
Subject(s) - medicine , metastasis , infiltration (hvac) , systemic administration , lymphokine activated killer cell , natural killer cell , pathology , nkg2d , peritoneal cavity , jugular vein , cancer research , interleukin 21 , immune system , biology , immunology , cytotoxic t cell , anatomy , t cell , cancer , in vivo , biochemistry , physics , microbiology and biotechnology , in vitro , thermodynamics
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 × 10 8 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/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 and 7 ± 4 A‐NK cells/mm 2 , respectively). No A‐NK cells were detected in the liver after i.p. injection. Rats bearing day 5 tumors were injected with 1.5 × 10 8 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.