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 following 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 labeled with the
fluorescent dye rhodamine (
TRITC) and next injected via a tail 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 administration of A-NK cells. At all time points tested, a significant linear relationship between the cross-section area of the
tumor and the number of infiltrating cells was observed, but small
tumor areas became fully infiltrated earlier than larger areas. At 24 hr after injection, approximately 10% of the injected cells were found in the
tumor tissue 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 cells per mm2 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, adoptively transferred A-NK cells are able to find and specifically infiltrate pulmonary
metastases in a time-dependent fashion.