In vivo system to detect long-term continuous release of bioactive interleukin-2 by immunopharmacological depot preparations in nude mice with human tumors.
For continuous release of cytokines for local application at tumor sites, we developed depot preparations consisting of a carrier substance (ethylene vinyl acetate copolymer) and either natural interleukin-2 (nIL-2) at 5 x 10(5) BRMP U or natural interferon-alpha (nIFN alpha) at 3 x 10(5) IU. We transplanted human tumors in nude mice and placed depot preparations next to the tumors to confirm the in vivo long-term biological activity of the depots according to the ability of IL-2 to inhibit growth of the tumors. Five different human tumors were used. Mice with each tumor were divided into groups of six to eight receiving different treatments: control (no treatment), human serum albumin, but no cytokine, IL-2 depot, IFN alpha depot and IFN alpha plus IL-2 depot. After proven in vivo tumor growth, these depot preparations were implanted subcutaneously directly at the tumor sites. Tumor growth was significantly reduced by IL-2 and IFN alpha plus IL-2 for 3 weeks after depot implantation. Complete tumor remission was not achieved. IFN alpha alone did not influence tumor growth. Our data show that the nude mouse is a valuable model for testing biological activity and release time of IL-2 depot preparations in vivo.
Huland
E
E
Department of Urology, University Clinic Eppendorf, Hamburg, Germany.
Falk
B
B
Hübner
D
D
Huland
H
H
D000818:Animals; D003692:Delayed-Action Preparations; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D014183:Transplantation, Heterologous
D003692:Delayed-Action Preparations; D016898:Interferon-alpha; D007376:Interleukin-2; D015375:Receptors, Interleukin-2