Biodistribution of radiolabelled human dendritic cells injected by various routes.
OBJECTIVE
The purpose of this study was to investigate the biodistribution of mature dendritic cells (DCs) injected by various routes, during a cell therapy protocol.


METHODS
In the context of a vaccine therapy protocol for melanoma, DCs matured with Ribomunyl and interferon-gamma were labelled with( 111)In-oxine and injected into eight patients along various routes: afferent lymphatic vessel (IL) (4 times), lymph node (IN) (5 times) and intradermally (ID) (6 times).


RESULTS
Scintigraphic investigations showed that the IL route allowed localisation of 80% of injected radioactivity in eight to ten nodes. In three cases of IN injection, the entire radioactivity stagnated in the injected nodes, while in two cases, migration to adjacent nodes was observed. This migration was detected rapidly after injection, as with IL injections, suggesting that passive transport occurred along the physiological lymphatic pathways. In two of the six ID injections, 1-2% of injected radioactivity reached a proximal lymph node. Migration was detectable in the first hour, but increased considerably after 24 h, suggesting an active migration mechanism. In both of the aforementioned cases, DCs were strongly CCR7-positive, but this feature was not a sufficient condition for effective migration. In comparison with DCs matured with TNF-alpha, IL-1beta, IL-6 and PGE2, our DCs showed a weaker in vitro migratory response to CCL21, despite comparable CCR7 expression, and higher allostimulatory and TH1 polarisation capacities.


CONCLUSIONS
The IL route allowed reproducible administration of specified numbers of DCs. The IN route sometimes yielded fairly similar results, but not reproducibly. Lastly, we showed that DCs matured without PGE2 that have in vitro TH1 polarisation capacities can migrate to lymph nodes after ID injection.
Quillien
Véronique
V
Centre Régional de Lutte Contre le Cancer, Rennes, France. v.quillen@rennes.fnclcc.fr
Moisan
Annick
A
Carsin
Andre
A
Lesimple
Thierry
T
Lefeuvre
Claudia
C
Adamski
Henri
H
Bertho
Nicolas
N
Devillers
Anne
A
Leberre
Claudine
C
Toujas
Louis
L
D000942:Antigens, Bacterial / Q000494:pharmacology; D019496:Cancer Vaccines; D002465:Cell Movement; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D064987:Cell- and Tissue-Based Therapy; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000166:cytology / Q000473:pathology*; D006801:Humans; D007118:Immunoassay; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy; D009362:Neoplasm Metastasis; D010641:Phenotype; D021122:Protein Subunits / Q000378:metabolism; D011877:Radionuclide Imaging; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D018417:Th1 Cells; D013997:Time Factors
D000942:Antigens, Bacterial; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D019496:Cancer Vaccines; D054421:Chemokine CCL21; D019742:Chemokines, CC; D021122:Protein Subunits; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C034206:Ribomunyl; D018664:Interleukin-12; D007371:Interferon-gamma