Interleukin-2 secretion by KHT sarcoma cells leads to loss of their vaccine potential

We have investigated the effect of interleukin-2 (IL-2) secretion by KHT sarcoma cells upon their vaccine potential in syngeneic C3Hf/He mice. Parental KHT tumor cells were transfected with the plasmid pBCMG-neo-mIL-2 to obtain a transfectant KHT-2-3-7 that secreted 20 units IL-2. KHT-2-3-7 cells elicited protective immunity in only 10% of the immunized mice, compared with 40% of mice immunized with irradiated parental KHT tumor colls. To minimize the contribution of potential antigenic differences between the KHT-2-3-7 transfectant and parental KHT cells, a clone of KHT cells (KHT-C21) was isolated and used in subsequent experiments. A number of transfectants secreting various amounts of IL-2, ranging from 2 units to 200 units, were obtained following transfection of KHT-C21 cells with plasmid pBCMG-neo-mIL-2. Two of the transfectants, C21-13-4 and C21-1, each secreting 200 units IL-2, elicited protective immunity in a significantly lower fraction of mice than did irradiated KHT-C21 parental tumor cells (P<0.01). Two other transfectants C21-10 and C21-11, secreting 2 and 23 units IL-2 respectively, also showed lower vaccine potential compared with the parental KHT-C21 clone (P<0.05). To minimize further any role for potential antigenic or other molecular differences between the individual transfectants and the clonal KHT-C21 parental cells in lowering their vaccine efficacy, mice were immunized with a mixture of five transfectants, and the results again showed significantly lower vaccine efficacy of the mixture compared with the irradiated parental C21 cells (P<0.01). In view of published studies showing enhanced or unchanged efficacy of IL-2-secreting tumor cell vaccines, our observation of the lower vaccine potential of IL-2-transduced tumor cells indicates that the vaccine efficacy of IL-2-secreting tumor cells depends on the individual tumor. Such variability/unpredictability would hamper the clinical use of IL-2-secreting tumor cells as vaccines.