Killing of autologous lymphoma by host human CD8⁺ T cells elicited by vaccination against idiotype

T cells are critical to the eradication of tumor cells in experimental model systems. However, the systematic demonstration of direct killing of patients' own, native tumor cells by human cytotoxic T lymphocytes (CTL) elicited by cancer vaccines has not been previously achieved. Here we demonstrate that CD8⁺ T cells isolated from 7 of 8 consecutive, unselected patients vaccinated against a self lymphoma antigen produced high levels of cytokines in a tumor-specific manner and in 6 cases each lysed unmodified, autologous tumor cells after a single cycle of restimulation in vitro. These responses were blocked by antibodies to MHC class I and were sustained for at least 6 months. Moreover, pre-vaccination peripheral blood mononuclear cells (PBMC) assayed in parallel under identical stimulation conditions failed to kill autologous lymphoma. Stimulation of immune PBMC with soluble tumor antigen also revealed the availability of antigen-specific CD4⁺ T cells to provide 'helper' function. These results provide formal proof that native, human tumor cells can serve as targets of a host T-cell response elicited by vaccination against a model antigen.