Immunotherapy of malignant melanoma in a SCID mouse model using the highly cytotoxic natural killer cell line NK-92.
In this work, we evaluated the potential of the natural killer (NK) cell line NK-92 and its IL-2-independent variants NK-92MI and CI, as immunotherapy for melanoma. In vitro, we found that NK-92 was much more cytotoxic to a number of human melanoma cell lines than lymphokine-activated killer (LAK) cells, particularly at low effector/target (E:T) ratios. In vivo treatment of mice challenged with MEWO melanoma cells with i.v. administered NK-92 and NK-92-MI resulted in a 1.5-2.5-fold increase in average length of survival. NK-92, MI, and CI were also effective against the WM1341 cell line, causing a 2-5-fold increase in survival when administered before the malignant cells. With s.c. injection, MEWO and WM1341 caused a primary tumor mass, secondary tumors, and metastatic cells. NK-92 cells reduced WM1341 primary tumor size by 40-90% and MEWO tumors by 30-75%. Similar results were seen with NK-92MI and CI. These data show that NK-92 cells are highly cytotoxic to human melanoma cells in vitro and in vivo and suggest that treatment with NK-92 cells may be a potentially effective immunotherapeutic modality in melanoma.
Department of Hematology, B.C. Cancer Agency, B.C. Cancer Research Centre, Vancouver, Canada.
Y K
YK
Tam
B
B
Miyagawa
V C
VC
Ho
H G
HG
Klingemann
D000818:Animals; D002460:Cell Line / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D014407:Tumor Cells, Cultured / Q000276:immunology