TUMOR-CELLS TRANSFECTED WITH A BACTERIAL HEAT-SHOCK GENE LOSE TUMORIGENICITY AND INDUCE PROTECTION AGAINST TUMORS

The gene encoding a highly immunogenic mycobacterial heat-shock protei n (hsp65) was transfected into the murine macrophage tumor cell line J 774. The resulting hsp65-expressing cells (J774-hsp65) were no longer able to produce tumors in syngeneic mice. This loss of tumorigenicity was not mediated through T cells since the transfected cells did not p roduce tumors in athymic mice. If mice are first immunized with the J7 74-hsp65 cells and then challenged with the parent J774 cells, the mic e do not develop tumors, indicating that the presence of the mycobacte rial hsp65 protein greatly enhances immunological recognition of uniqu e structures expressed by the parent tumor cells. This is further conf irmed by the demonstration in vitro of T cells derived from J774-hsp65 -immunized mice that are cytotoxic for the parent J774 cells. The resu lts provide the basis for a novel strategy for enhancing the immunolog ical recognition and decreasing the tumorigenicity of transformed cell s.