TY - JOUR
T1 - Clinical grade OK432-activated dendritic cells
T2 - In vitro characterization and tracking during intralymphatic delivery
AU - West, Emma
AU - Morgan, Ruth
AU - Scott, Karen
AU - Merrick, Alison
AU - Lubenko, Anatole
AU - Pawson, David
AU - Selby, Peter
AU - Hatfield, Paul
AU - Prestwich, Robin
AU - Fraser, Sheila
AU - Eves, David
AU - Anthoney, Alan
AU - Twelves, Chris
AU - Beirne, Debbie
AU - Patel, Poulam
AU - Odonnell, Dearbhaile
AU - Watt, Suzanne
AU - Waller, Michael
AU - Dietz, Allan
AU - Robinson, Philip
AU - Melcher, Alan
PY - 2009/1
Y1 - 2009/1
N2 - Dendritic cells (DC) are under intense preclinical and early clinical evaluation for the immunotherapy of cancer. However, the optimal culture conditions and route of delivery for DC vaccination have not been established. Here we describe the first human application of DC matured with the bacterial agent OK432 (OK-DC), using a short-term serum-free culture protocol, which generates mature DC from CD14 precursors after 5 days. These cells were prepared within the framework of a National Blood Service facility, demonstrating that DC represent a product which is potentially deliverable alongside current standardized cell therapies within the UK National Health Service. In vitro analysis confirmed that OK-DC were mature, secreted tumor necrosis factor-α, interleukin-6, and interleukin-12, and stimulated both T cell and natural killer cell function. To explore effective delivery of OK-DC to lymph nodes, we performed an initial clinical tracking study of radioactively labeled, unpulsed OK-DC after intralymphatic injection into the dorsum of the foot. We showed that injected DC rapidly localized to ipsilateral pelvic lymph nodes, but did not disseminate to more distant nodes over a 48-hour period. There was no significant toxicity associated with OK-DC delivery. These results show that OK-DC are suitable for clinical use, and that intralymphatic delivery is feasible for localizing cells to sites where optimal priming of innate and adaptive antitumor immunity is likely to occur.
AB - Dendritic cells (DC) are under intense preclinical and early clinical evaluation for the immunotherapy of cancer. However, the optimal culture conditions and route of delivery for DC vaccination have not been established. Here we describe the first human application of DC matured with the bacterial agent OK432 (OK-DC), using a short-term serum-free culture protocol, which generates mature DC from CD14 precursors after 5 days. These cells were prepared within the framework of a National Blood Service facility, demonstrating that DC represent a product which is potentially deliverable alongside current standardized cell therapies within the UK National Health Service. In vitro analysis confirmed that OK-DC were mature, secreted tumor necrosis factor-α, interleukin-6, and interleukin-12, and stimulated both T cell and natural killer cell function. To explore effective delivery of OK-DC to lymph nodes, we performed an initial clinical tracking study of radioactively labeled, unpulsed OK-DC after intralymphatic injection into the dorsum of the foot. We showed that injected DC rapidly localized to ipsilateral pelvic lymph nodes, but did not disseminate to more distant nodes over a 48-hour period. There was no significant toxicity associated with OK-DC delivery. These results show that OK-DC are suitable for clinical use, and that intralymphatic delivery is feasible for localizing cells to sites where optimal priming of innate and adaptive antitumor immunity is likely to occur.
KW - Dendritic cells
KW - Intralymphatic delivery
KW - NK cells
KW - OK432
KW - T cells
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U2 - 10.1097/CJI.0b013e31818be071
DO - 10.1097/CJI.0b013e31818be071
M3 - Article
C2 - 19307995
AN - SCOPUS:65549103031
SN - 1524-9557
VL - 32
SP - 66
EP - 78
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
IS - 1
ER -