Prevention of lethal tumor growth and generation of long-lasting immunity in vivo using CD137L and interleukin-12 gene transfer.
In a wide range of solid tumors, overexpression of CD137L has been shown to induce tumor immunity partly due to the stimulation of CD8+ CTL, which was even increased when immunotherapy with interleukin-12 (IL12) was additionally employed. However, little in known regarding hematologic neoplasias in this respect. Of the 8 animals receiving IL12-secreting tumor cells, 2 died. Animals treated with CD137L-expressing tumor cells and the combination group, all animals survived. Interestingly, re-challenge with wild-type tumor cells was rejected by all animals in the CD137L group and all remaining animals in the IL12 group, while these in the control group died. IL12- and CD137L-transfected plasmocytoma cells prevented tumor growth and induced long-lasting immunity. Our results warrant follow-up for future clinical use in patients with myeloma.
Kim
Young
Y
Department of Internal Medicine I, University Hospital Bonn, Germany.
Strehl
John W
JW
Gorschlüter
Marcus
M
Ziske
Carsten
C
Schmidt-Wolf
Ingo G H
IG
D053330:4-1BB Ligand / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D018274:Electroporation; D015316:Genetic Therapy; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D015996:Survival Rate
D053330:4-1BB Ligand; C505975:Tnfsf9 protein, mouse; D018664:Interleukin-12