Clinical trial of the intratumoral administration of labeled DC combined with systemic chemotherapy for esophageal cancer Journal Article
| Authors: | Fujiwara, S.; Wada, H.; Miyata, H.; Kawada, J.; Kawabata, R.; Nishikawa, H.; Gnjatic, S.; Sedrak, C.; Sato, E.; Nakamura, Y.; Sakakibara, M.; Kanto, T.; Shimosegawa, E.; Hatazawa, J.; Takahashi, T.; Kurokawa, Y.; Yamasaki, M.; Nakajima, K.; Takiguchi, S.; Nakayama, E.; Mori, M.; Doki, Y. |
| Article Title: | Clinical trial of the intratumoral administration of labeled DC combined with systemic chemotherapy for esophageal cancer |
| Abstract: | 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. © 2012 by Lippincott Williams & Wilkins. |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; human tissue; aged; human cell; cisplatin; doxorubicin; fluorouracil; cancer combination chemotherapy; cancer immunotherapy; dendritic cell; membrane proteins; enzyme linked immunosorbent assay; dendritic cells; cellular immunity; antigens, neoplasm; isotope labeling; cancer vaccines; lymph node; cell migration; preoperative treatment; radioimmunotherapy; esophagus cancer; indium 111; immunotherapy, adoptive; esophageal neoplasms; antigens, cd38; antibody production; cd83 antigen; esophageal cancer; scintigraphy; keyhole limpet hemocyanin; delayed hypersensitivity; skin test; indium; chemoimmunotherapy; intratumoral dc administration; dc migration; klh; ny-eso-1 specific t-cell response; dth; antibody against 28 tumor antigens; cd83 + cells |
| Journal Title: | Journal of Immunotherapy |
| Volume: | 35 |
| Issue: | 6 |
| ISSN: | 1524-9557 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2012-07-01 |
| Start Page: | 513 |
| End Page: | 521 |
| Language: | English |
| DOI: | 10.1097/CJI.0b013e3182619cb4 |
| PROVIDER: | scopus |
| PUBMED: | 22735809 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2012" - "CODEN: JOIME" - "Source: Scopus" |
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