Combination of local, nonviral IL12 gene therapy and systemic paclitaxel treatment in a metastatic breast cancer model
Repeated, local, nonviral IL12 (interleukin-12) gene delivery decreased tumor progression and increased immunogenicity. We combined our IL12 gene delivery with systemic paclitaxel chemotherapy as a treatment for paclitaxel (PCT)-resistant 4T1 subcutaneous mouse mammary carcinomas and PCT-sensitive, immunogenic/nonimmunogenic tumors. We mixed PCT with either a biodegradable polymeric solubilizer, HySolv, or Cremophor EL for bimonthly systemic treatments and injected water-soluble lipopolymer (WSLP)/p2CMVmIL-12 (plasmid encoding IL12 gene) complexes locally every week. We compared treated subcutaneous tumor volume and lung metastasis with controls. HySolv alone performed better compared to Cremophor EL in combination with WSLP/p2CMVmIL-12. We showed inhibition of 4T1 tumor growth and lung metastases in the combined WSLP/p2CMVmIL-12/HySolv group compared to the controls and the paclitaxel-only treated groups. In parallel experiments we also demonstrated additive responses for tumor growth and number of lung metastases within other PCT-sensitive mammary tumor models using this combination strategy. Our combination therapy provides evidence for the efficacy and feasibility of improved drug delivery systems. Local cytokine gene delivery can augment local and systemic chemotherapy without placing the host at risk for further systemic toxicity.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2004 |
|---|---|
| Erschienen: |
2004 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
|---|---|
| Enthalten in: |
Molecular therapy : the journal of the American Society of Gene Therapy - 9(2004), 6 vom: 15. Juni, Seite 829-36 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Janát-Amsbury, Margit Maria [VerfasserIn] |
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| Anmerkungen: |
Date Completed 13.01.2005 Date Revised 20.01.2017 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM148815227 |
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| 100 | 1 | |a Janát-Amsbury, Margit Maria |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Combination of local, nonviral IL12 gene therapy and systemic paclitaxel treatment in a metastatic breast cancer model |
| 264 | 1 | |c 2004 | |
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| 500 | |a Date Completed 13.01.2005 | ||
| 500 | |a Date Revised 20.01.2017 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Repeated, local, nonviral IL12 (interleukin-12) gene delivery decreased tumor progression and increased immunogenicity. We combined our IL12 gene delivery with systemic paclitaxel chemotherapy as a treatment for paclitaxel (PCT)-resistant 4T1 subcutaneous mouse mammary carcinomas and PCT-sensitive, immunogenic/nonimmunogenic tumors. We mixed PCT with either a biodegradable polymeric solubilizer, HySolv, or Cremophor EL for bimonthly systemic treatments and injected water-soluble lipopolymer (WSLP)/p2CMVmIL-12 (plasmid encoding IL12 gene) complexes locally every week. We compared treated subcutaneous tumor volume and lung metastasis with controls. HySolv alone performed better compared to Cremophor EL in combination with WSLP/p2CMVmIL-12. We showed inhibition of 4T1 tumor growth and lung metastases in the combined WSLP/p2CMVmIL-12/HySolv group compared to the controls and the paclitaxel-only treated groups. In parallel experiments we also demonstrated additive responses for tumor growth and number of lung metastases within other PCT-sensitive mammary tumor models using this combination strategy. Our combination therapy provides evidence for the efficacy and feasibility of improved drug delivery systems. Local cytokine gene delivery can augment local and systemic chemotherapy without placing the host at risk for further systemic toxicity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antineoplastic Agents, Phytogenic |2 NLM | |
| 650 | 7 | |a Lipids |2 NLM | |
| 650 | 7 | |a poly(ethylenimine)-co-(N-(2-aminoethyl) ethyleneimin)-co-N-(N-cholesteryloxycarbonyl-(2-aminoethyl)ethylenimine) |2 NLM | |
| 650 | 7 | |a Interleukin-12 |2 NLM | |
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| 650 | 7 | |a cremophor EL |2 NLM | |
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| 650 | 7 | |a Polyethyleneimine |2 NLM | |
| 650 | 7 | |a 9002-98-6 |2 NLM | |
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| 700 | 1 | |a Yockman, James W |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Minhyung |e verfasserin |4 aut | |
| 700 | 1 | |a Kern, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Furgeson, Darin Y |e verfasserin |4 aut | |
| 700 | 1 | |a Bikram, Malavosklish |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Sung Wan |e verfasserin |4 aut | |
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