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Neoadjuvant intratumoral cytokine-loaded microspheres are superior to postoperative autologous cellular vaccines in generating systemic anti-tumor immunity

dc.contributor.authorArora, Alishaen_US
dc.contributor.authorSu, Gangen_US
dc.contributor.authorMathiowitz, Edithen_US
dc.contributor.authorReineke, Joshuaen_US
dc.contributor.authorChang, Alfred E.en_US
dc.contributor.authorSabel, Michael S.en_US
dc.date.accessioned2007-09-20T16:41:45Z
dc.date.available2008-01-03T16:18:46Zen_US
dc.date.issued2006-10-01en_US
dc.identifier.citationArora, Alisha; Su, Gang; Mathiowitz, Edith; Reineke, Joshua; Chang, Alfred E.; Sabel, Michael S. (2006). "Neoadjuvant intratumoral cytokine-loaded microspheres are superior to postoperative autologous cellular vaccines in generating systemic anti-tumor immunity." Journal of Surgical Oncology 94(5): 403-412. <http://hdl.handle.net/2027.42/55822>en_US
dc.identifier.issn0022-4790en_US
dc.identifier.issn1096-9098en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/55822
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16967445&dopt=citationen_US
dc.description.abstractBackground Sustained intratumoral cytokine release using poly-lactic acid microspheres (PLAMs) can induce a systemic immune response, shifting immunotherapy to the neoadjuvant setting. Methods C57BL6 mice with established B16 melanomas underwent a single intralesional injection of IL-12, TNF-Α or GM-CSF PLAM, alone or in combination. Tumor draining lymph nodes (TDLN) and spleens were assessed for a specific anti-tumor response by IFNΓ release assay and ELISPOT. Results Intralesional injection of TNF-Α, alone or in combination, resulted in significant tumor ablation. The induction of tumor specific reactive T-cells in the TDLN was greatest with IL-12 and TNF-Α. Only mice treated with IL-12 and TNF-Α demonstrated a substantial T-cell response in cultured splenocytes. This combination resulted in a significant reduction in new tumors after re-challenge. Adjuvant therapy, using irradiated B16 cells in combination with equivalent doses of IL-12 and TNF-Α, failed to generate a similar T-cell response or prevent re-challenge. Conclusions Intratumoral IL-12 and TNF-Α loaded PLAM leads to both local eradication of tumor and the induction of specific anti-tumor T-cells in the lymph nodes and spleens, resulting in memory immune response. Neoadjuvant treatment was significantly superior to postoperative autologous cellular vaccines using IL-12 and TNF-Α PLAM. J. Surg. Oncol. 2006;94:403–412. © 2006 Wiley-Liss, Inc.en_US
dc.format.extent302090 bytes
dc.format.extent3118 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherLife and Medical Sciencesen_US
dc.subject.otherCancer Research, Oncology and Pathologyen_US
dc.titleNeoadjuvant intratumoral cytokine-loaded microspheres are superior to postoperative autologous cellular vaccines in generating systemic anti-tumor immunityen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelOncology and Hematologyen_US
dc.subject.hlbsecondlevelSurgery and Anesthesiologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDivision of Surgical Oncology, University of Michigan, Ann Arbor, Michiganen_US
dc.contributor.affiliationumDivision of Surgical Oncology, University of Michigan, Ann Arbor, Michiganen_US
dc.contributor.affiliationumDivision of Surgical Oncology, University of Michigan, Ann Arbor, Michiganen_US
dc.contributor.affiliationumDivision of Surgical Oncology, University of Michigan, Ann Arbor, Michigan ; 3304 Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0932. Fax: +734-647-9647.en_US
dc.contributor.affiliationotherDepartment of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Islanden_US
dc.contributor.affiliationotherDepartment of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Islanden_US
dc.identifier.pmid16967445en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/55822/1/20572_ftp.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1002/jso.20572en_US
dc.identifier.sourceJournal of Surgical Oncologyen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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