Immunotherapy of cancer using cytokine gene-modified tumor vaccines

Distant metastasis is the major cause for therapeutic failures in clinical oncology. Active immunotherapy of patients with low tumor burden would not only contribute to further reduction of the remaining tumor burden to subclinical levels, but it would also establish a constant state of immunity, i.e. immunological memory, that could protect the patient from recurrence of disease. Studies employing rodent tumor models with little or no intrinsic immunogenicity have shown that genitically modified tumor cell preparations consisting of irradiated tumor cells transduced with and expressing cytokines such as IL-2, IL-6, IFN-gamma or GM-CSF were capable of inducing the regression of a preexisting tumor burden and cure animals from their disease. Moreover, in some instances the cured animals have retained immunological memory, as indicated by the fact that such animals have resisted a second challenge with the parental tumor cells. Induction of potent immune responses in tumor bearing animals against non-immunogenic tumors supports the view that active immunization of cancer patients deserves consideration despite lack of demonstrable immunogenicity in many human tumors.