Oncogene-targeted antisense oligodeoxynucleotides combined with chemotherapy or immunotherapy: a new approach for tumor treatment?
Synthetic oligodeoxynucleotides (antisenses) complementary to bcr/abl breakpoint junction transcript on Philadelphia chromosome, or c-myb protooncogene inhibit partially the proliferation of Philadelphia positive leukemic cells (antisenses against bcr/abl and c-myb) and other tumor cells (antisenses against c-myb). This phenomenon is accompanied by specific downregulation of mRNA level of the particular gene. To develop a more effective procedure of tumor treatment the combination of low dose of cytostatic and bcr/abl or c-myb antisenses against Philadelphia chromosome positive cell line BV173, and the combination of anti-tumor cytotoxic T lymphocytes (CTL) and c-myb antisenses against melanoma cell line MM-28, were tested in vitro. Our results indicate that the combinations of conventional chemotherapeutic agent and antisense against bcr/abl or c-myb or tumor specific CTL and antisense against c-myb, are highly effective in killing of tumor cells and sparing normal cells. This creates the possibility to develop a more selective and effective treatment of neoplasia.
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107.
M
M
Nieborowska-Skórska
M
M
Nakashima
M
M
Ratajczak
Z
Z
Steplewski
B
B
Calabretta
T
T
Skórski
D001854:Bone Marrow Cells; D002455:Cell Division; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D009857:Oncogenes / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl