Tissue distribution of adoptively transferred adherent LAK cells: role of the route of administration.
The ability of LAK and adherent LAK (A-LAK) cells to migrate to and localize into tumors might be a limiting factor for the efficacy of adoptive immunotherapy. Employing different routes of inoculation of A-LAK cells labeled with 125IUdR, we have investigated how murine A-LAK cells circulate in the bloodstream and localize into various tissues. After intravenous injection, most of the A-LAK cells migrated to the lungs with less than 15% redistributing to other organs. Following left ventricular inoculation, after which the injected cells do not have to pass the lung capillaries before reaching other organs, higher numbers of A-LAK cells were found in liver, carcass, kidney and gut compared to intravenous injection. However, most of the A-LAK cells were cleared from these organs within 24 h, and surprisingly at this time the overall survival of the injected A-LAK cells was not more than 10-20% regardless of the route of injection. We found that a substantial accumulation of A-LAK cells in the liver could be achieved only when the cells were injected directly into the portal vein. Following this route of administration, more than 40% of the injected A-LAK cells were still in the liver at 24 h, whereas only 3-5% had redistributed to other organs. Our data suggest that A-LAK cells circulate inefficiently and survive poorly following systemic administration. However, enhanced accumulation of these cells in a particular organ might be achieved by direct administration of the A-LAK cells into the vessels feeding the organ.
Basse
P H
PH
Pittsburgh Cancer Institute, University of Pittsburgh, Pa.
Herberman
R B
RB
Hokland
M E
ME
Goldfarb
R H
RH
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000494:pharmacology; D007457:Iodine Radioisotopes; D015979:Killer Cells, Lymphokine-Activated / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011169:Portal Vein; D014018:Tissue Distribution
D007376:Interleukin-2; D007457:Iodine Radioisotopes