Linked Life Data

18049332

Source:http://linkedlifedata.com/resource/pubmed/id/18049332

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pubmed-article:18049332pubmed:abstractTextWe evaluated the impact and mechanism of interleukin (IL)-18 alone or in combination with IL-12 or tumor necrosis factor-alpha when delivered intratumorally via polylactic acid microspheres (PLAMs). C57BL6 mice with established B16 melanomas underwent a single intratumoral injection of IL-12, tumor necrosis factor-alpha, or IL-18 PLAM, alone or in combination. Tumor draining lymph nodes and splenocytes were assessed for specific antitumor response by FACS analysis and IFN-gamma release assay and enzyme-linked immunosorbent spot. Mice with established pulmonary metastases were killed for enumeration of pulmonary metastatic nodules after treatment of the primary tumor. Intratumoral treatment with IL-12 in combination with IL-18 led to significant tumor suppression compared with either cytokine alone. FACS analysis revealed the combination of IL-12 and IL-18 resulted in an increase in the percentage of CD3+ cells within the tumor draining lymph node, attributable to increases in both CD4+ and CD8+ T cells. Both IFN-gamma release assay and enzyme-linked immunosorbent spot demonstrated a significant and substantial increase in tumor-specific response with the combination. Treatment of the primary tumor with IL-12 and IL-18 PLAM led to a significant decrease in pulmonary metastases and improvement in survival compared with either cytokine alone. The systemic effects were abrogated after depletion of CD8+ or natural killer cells, but not CD4+ cells. IL-12 and IL-18, when released intratumorally in a sustained fashion as can be accomplished through the use of PLAM, demonstrate both local effects on tumor growth and the generation of a tumor-specific response capable of eradicating distant disease.lld:pubmed
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pubmed-article:18049332pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:18049332pubmed:articleTitleGeneration of a tumor-specific systemic response after intratumoral injection of IL-12 and IL-18-loaded polylactic acid microspheres.lld:pubmed
pubmed-article:18049332pubmed:affiliationDivision of Surgical Oncology, University of Michigan, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0932, USA. msabel@umich.edulld:pubmed
pubmed-article:18049332pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:18049332pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:18049332pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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