EXPERIMENTAL AND CLINICAL-STUDIES OF CYTOKINE GENE-MODIFIED TUMOR-CELLS

Cytokines are key modulators of host immune and inflammatory responses . The expression of cytokine genes by tumor cells as a result of gene transfer has emerged as a novel strategy to augment in vivo host react ivity to various cancers. This review summarizes the knowledge obtaine d from experimental systems using this strategy and provides informati on on the current clinical trials employing this approach. In murine m odel systems, immunization with tumors expressing certain cytokines [e .g., tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), in terleukin-7 (IL-7), and granulocyte-macrophage colony stimulating (GM- CSF)] has demonstrated their ability to promote the generation of tumo r-specific cytotoxic T lymphocytes by various mechanisms; in some case s, significant regressions of established microscopic tumor deposits r esult. Non T cell mechanisms of tumor killing, such as granulocytic in flammatory responses, may also be elicited by the localized elaboratio n of certain cytokines [e.g., IL4, granulocyte colony-stimulating fact or (G-CSF)]. The potency of antitumor immune potentiation by cytokines , however, remains to be established by further animal studies and eme rging clinical trials. The genetic modification of tumors for the expr ession of immunostimulatory gene products holds promise as a new appro ach for active immunotherapy of cancer and for the isolation of effect or cell populations for use in adoptive immunotherapy protocols.