Oncogene-targeted antisense oligodeoxynucleotides combined with chemotherapy or immunotherapy: a new approach for tumor treatment?

Folia Histochem Cytobiol. 1994;32(1):35-40. doi: 10.1007/BF02693351.

Abstract

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.

MeSH terms

  • Bone Marrow Cells
  • Cell Division
  • DNA, Neoplasm / genetics
  • Down-Regulation
  • Fusion Proteins, bcr-abl / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunotherapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Oligonucleotides, Antisense / therapeutic use*
  • Oncogenes / drug effects*
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • T-Lymphocytes, Cytotoxic / physiology*
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Fusion Proteins, bcr-abl