Growth inhibition of malignant CD5+B (B-1) cells by antisense IL-10 oligonucleotide.
Malignant B-1 cells derived from NZB mice, a murine model of chronic lymphocytic leukemia, produce significantly higher levels of IL-10 mRNA than normal B-1 or B cells. IL-10 may act as an autocrine growth factor for malignant B-1 cells. By addition of antisense oligodeoxynucleotides specific for IL-10 mRNA, we were able to dramatically inhibit the growth of leukemic B-1 cells in a time and dose dependent manner. Control cell lines which do not depend on IL-10 for growth were not affected. Antisense therapy targeted at the 5' region of the IL-10 mRNA not only resulted in inhibition of malignant B-1 cell proliferation but also inhibited IL-10 production by malignant B-1 cells. Because endogenous IL-10 gene activation is critical for B-1 cell expansion, inactivation of the endogenous IL-10 gene by IL-10 antisense rather than extracellular regulation of the IL-10 gene product should be successful in controlling the malignant growth.
Peng
B
B
Department of Pathology, UMDNJ-New Jersey Medical School, Newark 07103, USA.
Mehta
N H
NH
Fernandes
H
H
Chou
C C
CC
Raveché
E
E
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D001483:Base Sequence; D018956:CD5 Antigens; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006131:Growth Inhibitors; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018956:CD5 Antigens; D006131:Growth Inhibitors; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma