TY - JOUR
T1 - Local delivery of interleukin-2 and adriamycin is synergistic in the treatment of experimental malignant glioma
AU - Hsu, Wesley
AU - Lesniak, Maciej S.
AU - Tyler, Betty
AU - Brem, Henry
N1 - Funding Information:
This work was supported by the National Cooperative Drug Discovery Group of the National Cancer Institute (Grant U01-CA 52857), as well as a gift from the Lawrence Lomax Gift Fund. We thank Dr. Pamela Talalay for assistance in the preparation of the manuscript.
PY - 2005/9
Y1 - 2005/9
N2 - Introduction: Local delivery of adriamycin (ADR) via biodegradable polymers has been shown to improve survival in rats challenged intracranially with 9L gliosarcoma. Likewise, local delivery of interleukin-2 (IL-2) has been shown to extend survival in experimental brain tumor models. In the current study, we hypothesized that local delivery of ADR and IL-2 might act synergistically against experimental intracranial glioma. Methods: Polyanhydride polymers (PCPP-SA) containing 5% ADR by weight were prepared using the mix-melt method. IL-2 polymer microspheres (IL-2 MS) were produced via the complex coacervation of gelatin and chondroitin sulfate in the presence of IL-2. Sixty male Fisher 344 rats received an intracranial challenge with a lethal dose of 9L gliosarcoma cells. In addition, a group of rats were injected with either IL-2 MS or empty microspheres. Five days later they received ADR or blank polymer. There were a total of four treatment groups: (1) empty microspheres, blank polymer; (2) empty microspheres, ADR polymer; (3) IL-2 MS, blank polymer; and (4) IL-2 MS, ADR polymer. Results: Compared to control animals treated with empty microspheres and blank polymer, animals receiving empty microspheres and ADR polymer (P < 0.0004), IL-2 MS and blank polymer (P < 0.0005), and IL-2 MS combined with ADR polymer (P < 0.0000002) all showed statistically significant improvement in survival. In addition, animals receiving the IL-2/ADR combination had significantly extended survival compared to either ADR or IL-2 alone (P < 0.000003 and P < 0.0004, respectively). Conclusions: Both ADR and IL-2, when delivered locally, are effective monotherapeutic agents against experimental intracranial gliosarcoma. The combination ADR and IL-2 therapy is more effective than either agent alone.
AB - Introduction: Local delivery of adriamycin (ADR) via biodegradable polymers has been shown to improve survival in rats challenged intracranially with 9L gliosarcoma. Likewise, local delivery of interleukin-2 (IL-2) has been shown to extend survival in experimental brain tumor models. In the current study, we hypothesized that local delivery of ADR and IL-2 might act synergistically against experimental intracranial glioma. Methods: Polyanhydride polymers (PCPP-SA) containing 5% ADR by weight were prepared using the mix-melt method. IL-2 polymer microspheres (IL-2 MS) were produced via the complex coacervation of gelatin and chondroitin sulfate in the presence of IL-2. Sixty male Fisher 344 rats received an intracranial challenge with a lethal dose of 9L gliosarcoma cells. In addition, a group of rats were injected with either IL-2 MS or empty microspheres. Five days later they received ADR or blank polymer. There were a total of four treatment groups: (1) empty microspheres, blank polymer; (2) empty microspheres, ADR polymer; (3) IL-2 MS, blank polymer; and (4) IL-2 MS, ADR polymer. Results: Compared to control animals treated with empty microspheres and blank polymer, animals receiving empty microspheres and ADR polymer (P < 0.0004), IL-2 MS and blank polymer (P < 0.0005), and IL-2 MS combined with ADR polymer (P < 0.0000002) all showed statistically significant improvement in survival. In addition, animals receiving the IL-2/ADR combination had significantly extended survival compared to either ADR or IL-2 alone (P < 0.000003 and P < 0.0004, respectively). Conclusions: Both ADR and IL-2, when delivered locally, are effective monotherapeutic agents against experimental intracranial gliosarcoma. The combination ADR and IL-2 therapy is more effective than either agent alone.
KW - Adriamycin
KW - Biodegradable polymer
KW - Brain tumor
KW - Cytokine
KW - Interleukin-2
KW - Interstitial chemotherapy
KW - Microspheres
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U2 - 10.1007/s11060-004-6597-8
DO - 10.1007/s11060-004-6597-8
M3 - Article
C2 - 16193383
AN - SCOPUS:26944451593
SN - 0167-594X
VL - 74
SP - 135
EP - 140
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 2
ER -
