Epstein-Barr virus (EBV)-based expression vectors were tested for
cytokine gene transfer-mediated induction of an immune response against human
lymphoma cells. These vectors express the EBV latent gene
EBNA 1 and carry the EBV latent origin of replication (ori P) for episomal replication in transfected cells. In addition, 3 human
immunoglobulin light chain enhancer elements augment expression in B-cells. The suitability of these vectors for expression of
cytokine genes in human
lymphoma cells in vitro has been demonstrated. In order to extend these experiments in vivo, highly tumorigenic
Burkitt's lymphoma (BL) cells were transfected with different
cytokine genes of human and murine origin cloned into the
EBNA 1/ori P vectors. Tumorigenicity of the transfectants was measured after inoculation into nude mice. No effect on tumorigenicity was observed after hIL 6 transfection and an inconsistent effect after hTNFalpha transfection. In contrast, complete suppression of
tumor outgrowth occurred in hIL 10 transfectants. This
tumor suppressive effect, however, was restricted to the IL 10 transfectants themselves and not directed against non-transfected cells. By comparison,
mIL 4 transfected BL cells also were non-tumorigenic. However, co-inoculation of
mIL 4 transfected and non transfected cells resulted in suppression of the tumorigenicity of the non-transfected cells. Thus, highly tumorigenic BL cells in nude mice are sensitive to immune effector mechanisms triggered by
cytokine expression. In this experimental model,
EBNA 1/ori P expression vectors are a suitable tool for
cytokine gene transfer mediated induction of an anti-
lymphoma immune response of the host.