EFFICIENT TRANSDUCTION OF EARLY-PASSAGE HUMAN-MELANOMA TO SECRETE IL-4

Augmentation of tumor immunogenicity has been increasingly studied as a strategy to develop host immunity against established malignancies. Genetic modification of tumors to secrete immunoregulatory peptides su ch as IL-4 has been demonstrated to augment tumor immunogenicity and e nhance the induction of tumor reactive lymphoid cells in animal models . To explore the ability of IL-4 to augment the immunogenicity of mela noma cells, we constructed a recombinant retrovirus vector encoding fo r human IL-4 and used it to transduce human melanomas. After optimizin g retrovirus transduction conditions using a reporter virus, an IL-4 e ncoding retrovirus vector was used to transduce early and late passage melanoma cells. IL-4 production rates of up to 2000 pg/ml per 24 h pe r 10(6) cells were achieved, and provirus could be detected by Souther n blot of the transduced cells at 0.1 copies per cell. The IL-4 produc ed by the melanoma cells was biologically active. Irradiated transduce d melanoma cells continued to produce IL-4 for at least two weeks of o bservation. Thus melanoma cells can be efficiently modified to secrete biologically active IL-4, and may be suitable substrates for autologo us tumor cell vaccines.