Clinical trial of the intratumoral administration of labeled DC combined with systemic chemotherapy for esophageal cancer.
Esophageal cancer is a highly aggressive disease, and improved modalities for its treatment are needed. We performed chemoimmunotherapy involving the intratumoral administration of 111In-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 111In-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.
Department of Gastroenterological Surgery, Osaka University, Osaka, Japan.
Shinichi
S
Fujiwara
Hisashi
H
Wada
Hiroshi
H
Miyata
Junji
J
Kawada
Ryohei
R
Kawabata
Hiroyoshi
H
Nishikawa
Sacha
S
Gnjatic
Christine
C
Sedrak
Eiichi
E
Sato
Yurika
Y
Nakamura
Mitsuru
M
Sakakibara
Tatsuya
T
Kanto
Eku
E
Shimosegawa
Jun
J
Hatazawa
Tsuyoshi
T
Takahashi
Yukinori
Y
Kurokawa
Makoto
M
Yamasaki
Kiyokazu
K
Nakajima
Shuji
S
Takiguchi
Eiichi
E
Nakayama
Masaki
M
Mori
Yuichiro
Y
Doki
D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology*; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007204:Indium; D008565:Membrane Proteins / Q000276:immunology; D016499:Radioimmunotherapy
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins; D007204:Indium; D051997:ADP-ribosyl Cyclase 1