Controlled local delivery of interleukin-2 by biodegradable polymers protects animals from experimental brain tumors and liver tumors.

Published

Journal Article

PURPOSE:The purpose of our study was to develop an injectable polymeric system for the long-term localized delivery of bioactive interleukin-2 for antitumor immunotherapy. METHODS:IL-2 was encapsulated into gelatin and chondroitin-6-sulfate using an aqueous-based complex coacervation. CTLL-2 cells were used to measure the bioactivity of released IL-2 and radiolabeled IL-2 was used for release studies in the rat brain and mouse liver. Antitumor efficacy studies were carried out in primary (9L gliosarcoma) and metastatic (B16-F10 melanoma) brain tumor models in rats and mice, respectively, as well as a murine liver tumor model (CT26 carcinoma). Survivors of the metastatic brain tumor challenge were rechallenged with tumor in the opposite lobe of the brain to confirm that antitumor immunologic memory had developed. RESULTS:Bioactive IL-2 was released for over 2 weeks in vitro and in vivo IL-2 release showed significant IL-2 levels for up to 21 days. Polymeric IL-2 microspheres injected intratumorally were statistically more effective in protecting animals challenged with fatal tumor doses in the brain and the liver than placebo or autologous tumor cells genetically engineered to secrete IL-2. Immunologic memory was induced following IL-2 microsphere therapy in the B16-F10 brain tumor model that was capable of protecting 42% of animals from a subsequent intracranial tumor challenge, suggesting that tumor destruction was mediated by the immune system. CONCLUSIONS:Local IL-2 therapy using novel polymeric carriers. aimed at stimulating long-lasting antitumor immunity, may provide an improved method of treating a variety of cancers.

Full Text

Cited Authors

  • Hanes, J; Sills, A; Zhao, Z; Suh, KW; Tyler, B; DiMeco, F; Brat, DJ; Choti, MA; Leong, KW; Pardoll, DM; Brem, H

Published Date

  • July 2001

Published In

Volume / Issue

  • 18 / 7

Start / End Page

  • 899 - 906

PubMed ID

  • 11496947

Pubmed Central ID

  • 11496947

Electronic International Standard Serial Number (EISSN)

  • 1573-904X

International Standard Serial Number (ISSN)

  • 0724-8741

Digital Object Identifier (DOI)

  • 10.1023/a:1010963307097

Language

  • eng