IMMUNE-REACTIONS INDUCED BY INTERLEUKIN-2 TRANSFECTED COLORECTAL-CANCER CELLS IN-VITRO - PREDOMINANT INDUCTION OF LYMPHOKINE-ACTIVATED KILLER-CELLS

One aim of the genetic modification of tumor cells is the generation o f immunogenic variants that can be used for the induction of immune re sponses against tumors. We engineered the human colorectal carcinoma c ell line SW480 by means of plasmid transfection to secrete interleukin (IL)-2. Transfection of SW480 cells resulted in stable IL-2 secretion at 5-30 ng/ml per 10(5) cells in 24 h and, unexpectedly, in CD54 expr ession on the cell surface. SW480 variants expressing IL-2 and CD54 we re tested for their capacity to induce T lymphocyte activation in vitr o in comparison to untransfected and CD54 transfected eels. The cytoly tic effector function of a class I MHC restricted CD8(+), peptide anti gen specific T cell clone was augmented following expression of CD54. IL-2 secreting SW480 variants did not further increase antigen-depende nt cytolysis. Primary activation of resting T lymphocytes was assessed following allogeneic stimulation. When compared with unmodified SW480 cells, CD54 expressing variants did not initiate T cell proliferation . In contrast, IL-2 secreting SW480 cells strongly promoted primary T cell proliferation. Similarly, exogenous IL-2 and SW480 cells induced T cell proliferation which was not only due to IL-2 but was dependent on tumor cells. However, following the initial wave of cell growth in response to IL-2 secreting SW480 cells T lymphocytes could not be rest imulated with SW480 or IL-2 secreting variants and could not be furthe r expanded. T cells initially activated by IL-2 secreting SW480 cells exhibited cytolytic activity towards SW480 cells. This reactivity, how ever, was transient and completely blocked by K562 cells, suggesting M HC-unrestricted, nonspecific cytotoxicity. We conclude that endogenous IL-2 secretion by the colorectal carcinoma cell line SW480 does not r esult in the activation of MHC restricted specific T lymphocytes but p redominantly induces lymphokine-activated killer cells. Considering th at tumor cell vaccines are aimed at inducing tumor-specific immune res ponses, our in vitro observation would rather argue against the in viv o application of such a tumor cell modification in colorectal cancer.