| Clinical Trial of the Intratumoral Administration of Labeled DC Combined With Systemic Chemotherapy for Esophageal Cancer. | |
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MedLine Citation:
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PMID: 22735809 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Esophageal cancer is a highly aggressive disease, and improved modalities for its treatment are needed. We performed chemoimmunotherapy involving the intratumoral administration of In-labeled dendritic cells (DC) in combination with preoperative chemotherapy in 5 esophageal cancer patients. Mature DC were generated and traced by scintigraphy after their administration. No adverse events that were directly related to the intratumoral DC administration were observed. Delayed-type hypersensitivity skin tests against keyhole limpet hemocyanin, which was added to the culture medium, detected a positive response in 3 patients, and keyhole limpet hemocyanin antibody production was observed in 4 patients, suggesting that intratumorally administered DC migrate to the lymph nodes, where they function as antigen-presenting cells. However, scintigraphic images obtained after the DC administration demonstrated that the DC remained at the esophageal tumor injection sites in all cases, and no DC accumulation was observed elsewhere. The accumulation of CD83 cells in the primary tumor was also observed in 2 out of 4 patients in an immunohistochemical analysis using surgically resected specimens. Although the induction of tumor-specific immune responses during chemoimmunotherapy was also analyzed in enzyme-linked immunosorbent assay against 28 tumor antigens, none of the antibodies against the antigens displayed enhanced titers. No changes of NY-ESO-1-specific cellular immune response was observed in a patient who displayed NY-ESO-1 antibody production before the DC administration. These results suggest that the intratumoral administration of In-labeled mature DC during chemotherapy does not lead to detectable DC migration from the primary tumor to the draining lymph nodes, and therefore, might not achieve an optimal clinical response. |
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Authors:
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Shinichi Fujiwara; Hisashi Wada; Hiroshi Miyata; Junji Kawada; Ryohei Kawabata; Hiroyoshi Nishikawa; Sacha Gnjatic; Christine Sedrak; Eiichi Sato; Yurika Nakamura; Mitsuru Sakakibara; Tatsuya Kanto; Eku Shimosegawa; Jun Hatazawa; Tsuyoshi Takahashi; Yukinori Kurokawa; Makoto Yamasaki; Kiyokazu Nakajima; Shuji Takiguchi; Eiichi Nakayama; Masaki Mori; Yuichiro Doki |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of immunotherapy (Hagerstown, Md. : 1997) Volume: 35 ISSN: 1537-4513 ISO Abbreviation: J. Immunother. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-06-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9706083 Medline TA: J Immunother Country: United States |
Other Details:
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Languages: eng Pagination: 513-21 Citation Subset: IM |
Affiliation:
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Departments of *Gastroenterological Surgery ∥Gastroenterology and Hepatology ¶Nuclear Medicine, Graduate School of Medicine †Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka §Department of Pathology, Tokyo Medical University, Tokyo #Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki, Japan ‡New York Branch at the Memorial Sloan-Kettering Cancer Center, Ludwig Institute for Cancer Research, New York, NY. |
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