A Model for the Assessment of Human Recombinant Interleukin 2 (RIL2) Coated Erythrocytes as a Delivery System for Immunotherapy

Abstract

A carrier system for IL2 is needed in order to circumvent the toxicity associated with high dose interleukin 2 (IL2) administration and its rapid clearance from circulation. Erythrocytes (RBC) 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 RBC coated with rIL2 (RBC-rIL2) induce cytotoxicity (21–31%) 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 tumor size as compared to 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 per 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.