CHARACTERIZATION AND TUMORIGENICITY OF HUMAN NEUROBLASTOMA-CELLS TRANSFECTED WITH THE IL-2 GENE

Immunization of cancer patients with cytokine-engineered tumor cells i s being currently tested in several trials. To test the feasibility of this approach in neuroblastoma (NB) patients we investigated the func tional consequences of interleukin-2 (IL-2) gene transfer into NE cell lines. Two human NE cell lines were transfected with the plasmid expr ession vector RSV.5neo containing the human IL-2 cDNA, and their tumor igenicity was evaluated in a nude mice xenograft model after character ization of the growth patterns and phenotypic features in vitro. The c ombination of IL-2 gene transfection and the xenograft model in nude n ice was chosen on the basis of the low or absent expression of HLA cla ss I antigen in human NE tumors. Our aim was to evaluate the effective ness of an immunization protocol that could elicit a nonspecific antit umor response. The IL-2 stable transfectants were morphologically iden tical to parental or vector-transfected cells but completely lost tumo rigenicity and inhibited, through a bystander effect, the growth of pa rental cells injected simultaneously at the same site. Histologic and immunohistochemical analysis of the nodules showed extensive necrosis with severe endothelial damage. The infiltrating cells were mainly mac rophages, while natural killer(NK) cells were scarce. However, depleti on of NK cells by anti-CD122 monoclonal antibody indicated that the re jection process required NK cell activity. The relevance of these data for the development of therapeutic approaches using cytokine-engineer ed NE cell lines is discussed.