Enhanced biological activity of human recombinant interleukin 2 coupled to mouse red blood cells as evaluated using the mouse Meth A sarcoma model

Abstract

In order to circumvent the toxicity associated with high-dose interleukin 2 (IL2) administration and its rapid clearance from the circulation, a carrier system for IL2 is needed. Red blood cells (RBCs) coated with recombinant interleukin 2 (rIL2) provide a means of delivering IL2 into the system in a continuous low-dose manner which, in turn, maintains a low, potentially non-toxic, IL2 concentration. Murine RBCs coated with rIL2 (RBCs-rIL2) are able to induce cytotoxic activity in mouse spleen cells in vitro against malignant murine YAC-1 cells (53-62% cytotoxicity) using less than 4500 i.u./10(9) RBCs per mouse. Cytotoxicity (21-31%) becomes apparent upon cytotoxic testing of spleens cells stimulated in vivo. Using the murine Meth A sarcoma model, the effectiveness of this RBC-rIL2 vehicle is demonstrated in vivo by a 84% reduction in tumour size as compared with the soluble-rIL2-treated mice. Moreover, the RBC-rIL2 vehicle is able to induce tumoricidal cytotoxicity with very low rIL2 concentrations (about 10,000 i.u. of rIL2/mouse). These results indicate that rIL2 retains its biological activity when bound to the RBC and therefore could prove useful as a therapeutic delivery system for cancer treatment.