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Related Experiment Videos

Antisense therapy of hematologic malignancies.

F E Cotter1

  • 1Department of Experimental Hematology, St. Bartholomew Royal London School of Medicine, UK.

Seminars in Hematology
|October 26, 1999
PubMed
Summary

Bcl-2 antisense oligonucleotide (AO) therapy targets gene expression in lymphoma cells, showing efficacy and low toxicity. This approach offers a promising new treatment for refractory lymphomas and other malignancies.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tumor cells often exhibit inherent resistance to treatment due to altered gene expression.
  • Targeting specific genes like Bcl-2 offers a strategy to eradicate malignant cells by exploiting these differences.

Purpose of the Study:

  • To evaluate the efficacy and safety of Bcl-2 antisense oligonucleotide (AO) therapy in lymphoma.
  • To explore the potential of AO therapy in overcoming chemoresistance and treating refractory malignancies.

Main Methods:

  • Utilized Bcl-2 antisense oligonucleotide (AO) therapy, specifically G3139, to target the Bcl-2 gene.
  • Conducted preclinical toxicity studies and a Phase I clinical trial with dose escalation.
  • Investigated AOs targeting Bcl-X(L), protein kinase-Calpha (PKCalpha), and MDM2 genes.

Main Results:

  • G3139 demonstrated good tolerance in preclinical studies and was well-tolerated with minimal toxicity in a Phase I clinical trial.
  • A complete clinical and radiologic response lasting over 2 years was observed in a patient with stage IVB follicular lymphoma.
  • Reversible thrombocytopenia was identified as the main dose-limiting toxicity.

Conclusions:

  • Downregulation of antiapoptotic genes using AOs shows low toxicity and significant antilymphoma activity, particularly in cases resistant to conventional chemotherapy.
  • AO therapy holds promise for overcoming chemoresistance and may be combined with chemotherapy for effective treatment of various malignancies.
  • Further development of antisense reagents targeting other genes (Bcl-X(L), PKCalpha, MDM2) is ongoing for non-Hodgkin's lymphoma and other cancers.

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