THE INFILTRATION OF EXPERIMENTALLY-INDUCED LUNG METASTASES OF COLON-CARCINOMA CC531 BY ADOPTIVELY TRANSFERRED INTERLEUKIN-2-ACTIVATED NATURAL-KILLER-CELLS IN WAG RATS

The number of IL-2-activated natural killer (A-NK) cells reaching the tumor site in vivo may be crucial for their anti-tumor effect followin g adoptive immunotherapy. We investigated in a syngeneic rat model the infiltration of established lung metastases by adoptively transferred A-NK cells. The Wag rat colon carcinoma CC531 was injected via a tail vein to induce pulmonary metastases. Syngeneic A-NK cells were labele d with the fluorescent dye rhodamine (TRITC) and next injected via a t ail vein in rats bearing day-12 lung tumors. The number of A-NK cells in tumor and in normal tissue per rat was counted in sections after ad ministration of A-NK cells. At all time points tested, a significant l inear relationship between the cross-section area of the tumor and the number of infiltrating cells was observed, but small tumor areas beca me fully infiltrated earlier than larger areas. At 24 hr after injecti on, approximately 10% of the injected cells were found in the tumor ti ssue and the average A-NK-cell-to-tumor-cell ratio was estimated to be 1:3. A-NK cells were found in the liver too, although the number of c ells per mm(2) tissue was low compared with the pulmonary tumor tissue . Very low numbers of A-NK cells were found in kidney, adrenal gland, spleen, and blood. We conclude that, in this syngeneic rat model, adop tively transferred A-NK cells are able to find and specifically infilt rate pulmonary metastases in a time-dependent fashion. (C) 1994 Wiley- Liss, Inc.