Experimental Gene Therapy for Cancer Using Tumor Cells Engineered to Secrete Interleukin-15

Interleukin (IL)-15 is a recently described cytokine which resembles IL-2 in its biological activities, including stimulating T-cell and NK-cell proliferation and activation as well as enhancing B-cell expansion and antibody production. IL-2 is produced by helper T-cells, while IL-15 is produced by a wide variety of tissues including activated monocytes/macrophages. The difference in the expression pattern between IL-2 and IL-15 suggests unique in vivo roles for IL-15. To investigate the influence of localized secretion of IL-15 on tumor cell growth, the gene for human IL-15 was introduced into Meth-A cells with expression vector, pRC/CMV, and the ability of transfected cells to form tumors in vivo was evaluated. In BALB/C mice IL-15-transfected Meth-A cells (Meth-A/IL-15) were completely rejected, while Meth-A cells transfected with vector alone (Meth-A/Neo) grew rapidly. However, in BALB/c-nu/nu mice Meth-A/IL-15 did not show any gross difference in growth rate compared with Meth-A/Neo. Histological examination of the site of injection of Meth-A/IL-15 in BALB/C mice showed predominant mononuclear cell infiltration accompanied with neutrophilic infiltration, while BALB/c-nu/nu mice showed few mononuclear and neutrophilic cell infiltration. Moreover, the rejection of rechallenged parental Meth-A cells indicated the development of systemic and specific immunity to the parental tumor. These results suggest that IL-15-secreting tumor cells are capable of stimulating the growth of local and systemic T-cell-dependent immunity associated with local neutrophilic infiltration, and that gene therapy using IL-15 secreting tumor cells may be a new strategy for cancer therapy.

インターロイキン-15

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