Interleukin-2 gene transfer into human transitional cell carcinoma of the urinary bladder

Transitional cell carcinoma of the bladder is one of the human cancers most responsive to immunotherapy, and local interleukin-2 (IL-2) production app ears to be an important requirement for immunotherapy to he effective, in t his study, we engineered two human bladder cancer cell lines (RT112 and EJ) to constitutively release human IL-2 by retroviral vector-mediated gene tr ansfer. Following infection and selection, stable and consistent production of biologically active IL-2 was demonstrated at both the mRNA and the prot ein level. Morphology, in vitro growth rate and proliferation, as well as o ther cytokine gene mRNA or membrane adhesion receptor expression, were not altered in IL-2 transduced cells as compared to their parental or control v ector-infected counterparts. Moreover, IL-2 engineered cells lost their tum origenicity into nu/nu mice and the mechanism of rejection appeared to invo lve multiple host effector cell populations, among which a prominent role w as played by neutrophils and radiosensitive cells. These findings may offer support to the development of an IL-2-based gene therapy approach to human bladder cancer.